Molecularly Imprinted Polymer Sensor Research Articles

Integrating fluorescent molecularly imprinted polymer (MIP) sensor particles with a modular microfluidic platform for nanomolar small-molecule detection directly in aqueous samples

Fluorescent sensory MIP (molecularly imprinted polymer) particles were combined with a droplet-based 3D microfluidic system for the selective determination of a prototype small-molecule analyte of environmental concern, 2,4-dichlorophenoxyacetic acid or 2,4-D, at nanomolar concentration directly in water samples. A tailor-made fluorescent indicator cross-linker was thus designed that translates the binding event directly into an enhanced fluorescence signal. The phenoxazinone-type cross-linker was co-polymerized into a thin MIP layer grafted from the surface of silica microparticles following a RAFT (reversible addition-fragmentation chain transfer) polymerization protocol. While the indicator cross-linker outperformed its corresponding monomer twin, establishment of a phase-transfer protocol was essential to guarantee that the hydrogen bond-mediated signalling mechanism between the urea binding site on the indicator cross-linker and the carboxylate group of the analyte was still operative upon real sample analysis. The latter was achieved by integration of the fluorescent core-shell MIP sensor particles into a modular microfluidic platform that allows for an in-line phase-transfer assay, extracting the analyte from aqueous sample droplets into the organic phase that contains the sensor particles. Real-time fluorescence determination of 2,4-D down to 20nM was realized with the system and applied for the analysis of various surface water samples collected from different parts of the world.

Electrochemical and piezoelectric monitoring of taurine via electropolymerized molecularly imprinted films.

A molecularly imprinted electrochemical quartz crystal microbalance (EQCM) sensor is fabricated here for taurine, a β-amino acid significant for functioning of almost all vital organs. The polymeric film of l-methionine was electrochemically deposited on gold-coated EQCM electrode. Experimental parameters were optimized for controlling the performance of molecularly imprinted polymer (MIP)-modified sensor such as ratio of monomer and template, number of electropolymerization cycles, mass deposited in each cycle, and pH. Thus, fabricated MIP-EQCM sensor was successfully applied for estimation of taurine in solutions with varying matrices, such as aqueous, human blood plasma, milk from cow, buffalo, and milk powder. Under optimized parameters, response of MIP sensor to taurine was linearly proportional to its concentration with limit of detection as 0.12μM. Hence, a highly sensitive and selective piezoelectric sensor for taurine has been reported here via imprinting approach.

A novel molecularly imprinted electrochemical sensor modified with carbon dots, chitosan, gold nanoparticles for the determination of patulin

In this paper, molecular imprinting technique was applied to the electrochemical sensor. We used 2-oxindole as dummy template, ρ-Aminothiophenol (ρ-ATP) as functional monomers, combined with the high sensitivity of electrochemical detection, to achieve a specific and efficient detection of patulin in fruit juice. In addition, carbon dots and chitosan were used as the modifying material to improve electron-transfer rate, expand the electroactive surface of glassy carbon electrode and enhance strength of the signal. The Au–S bond and hydrogen bond were employed to complete the assembly of the ρ-ATP and 2-oxindole on the surface of the electrode. Then, polymer membranes were formed by electropolymerization in a polymer solution containing ρ-ATP, HAuCl4, tetrabutylammonium perchlorate (TBAP) and the template molecule 2- oxindole. After elution, the specific cavity can adsorb the target patulin. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements were performed to monitor the electropolymerization process and its optimization. Transmission electron microscopy (TEM), Scanning electron microscopy (SEM) and Atomic force microscopy (AFM) analyses were used for characterization. This was the first time that the molecularly imprinted polymer (MIP) technology combined with carbon dots, chitosan and Au nanoparticles modification and was applied in the electrochemical detection of patulin. The linear response range of the MIP sensor was from 1 × 10–12 to 1 × 10−9molL−1 and the limit of detection (LOD) was 7.57 × 10–13molL−1. The sensor had a high-speed real-time detection capability, low sample consumption, high sensitivity, low interference, good stability and could become a new promising method for the detection of patulin.

Synthesis of Molecularly Imprinted Polymer via Visible Light Activated RAFT Polymerization in Aqueous Media at Room Temperature for Highly Selective Electrochemical Assay of Glucose

The mild environment where most proteins and antibodies in living systems are prepared has inspired fascination among chemists. Herein, a new, rapid, low‐cost, and environment‐friendly method is proposed to synthesize molecularly imprinted polymers (MIPs) via visible light activated reversible addition–fragmentation chain transfer polymerization in aqueous media at room temperature for highly selective electrochemical assay of glucose. The MIPs with microsphere morphology, the better hydraulic distribution, large surface area, uniform large pore sizes, and high pore volume exhibit a significant adsorption efficiency compared with nonimprinted polymers for glucose. In addition, the MIP sensor recognizing the glucose significantly exceeds that of the other saccharide analogs, possesses regenerative ability, and presents high sensitivity by applying for the detection of glucose in human urine samples.

Electrochemical sensor for dodecyl gallate determination based on electropolymerized molecularly imprinted polymer

An electrochemical sensor based on molecularly imprinted polymer (MIP) film for dodecyl gallate detection at the surface of a glassy carbon electrode (GCE) was proposed in this paper. The GCE was modified with f-MWCNT and the MIP synthesis was performed in situ by means of electropolymerization using ortho-phenylenediamine as the monomer. The stepwise preparation of the MIP and NIP (non-imprinted polymer) was characterized electrochemically by means of cyclic and square wave voltammetry employing ferrocyanide/ferricyanide as a redox probe. The selective capacity performance of the MIP and its imprinted effect to the template molecule (analyte) was compared to the NIP. They were also characterized by scanning electron microscopy technique (SEM). The analytical performance of the MIP sensor performed using square wave voltammetry showed linear range from 0.50 to 8.0×10−9molL−1, with a correlation coefficient of 0.9921. The sensor presented detection and quantification limit of 0.22×10−9 and 0.67×10−9molL−1, respectively. The apparent dissociation constant (KD) calculated was of 1.26×10−4molL−1 and 5.27×10−1molL−1 for the MIP and NIP respectively.

Determination of methimazole based on electropolymerized-molecularly imprinted polypyrrole modified pencil graphite sensor

Preparation of a molecularly imprinted polymer (MIP) film and its recognition property for methimazole (MMZ) was investigated. The polypyrrole (PPy) film was prepared by the cyclic voltammetric deposition of pyrrole in the presence of a supporting electrolyte (NaClO4·H2O) with and without MMZ through on a pencil graphite electrode (PGE). A computational study based on density functional theory was developed to evaluate the template-monomer geometry and interaction energy in the prepolymerization mixture. The performance of MIP sensor and non-imprinted polymer (NIP) film was evaluated by differential pulse voltammetry (DPV). The most important parameters controlling the performance of sensor were investigated and optimized. The prepared electrode was used for MMZ measurement by a three-step procedure, including analyte extraction in the electrode, electrode washing and electrochemical measurement of MMZ. The molecularly imprinted film exhibited a high selectivity and sensitivity toward methimazole in the experimental conditions. The calibration curve demonstrated linearity over a concentration range of 0.007–6mM with a correlation coefficient (r2) of 0.9808. The accuracy of the method was studied through spiking blank samples showed recovery of 98% with precision of 4%. Limit of detection based on S/N=3 was obtained 3×10−6M. The proposed sensor was applied successfully to determine MMZ in biological model samples and pharmaceuticals.

Experimental design-artificial neural network-genetic algorithm optimization and computer-assisted design of celecoxib molecularly imprinted polymer/carbon nanotube sensor

A molecularly imprinted polymer (MIP) sensor was prepared applying electropolymerization of pyrrole monomer in the presence of celecoxib (CXB) as a template molecule on a pencil graphite electrode (PGE) which modified with functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication of sensor and the measurement process were carried out by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) method, respectively. The selection of functional monomer was done using computational method. The optimization of parameters was performed using Plackett–Burman design (PBD), central composite design (CCD), artificial neural network (ANN) and genetic algorithm (GA). First, a Plackett–Burman design as a screening method was applied to estimate positive or negative influences of the factors on the sensor response. In the next step of optimization process, significant factors affecting the performance of the MIP sensor were investigated using CCD. The data from CCD used to train the ANN using Bayesian regularization. The ANN was trained with mean square error (MSE) of 0.0336. The predicted model obtained from the trained ANN was introduced to GA as the fitness function to be optimized. GA optimized the fitness function using the defined constraints. Under the obtained optimal conditions a linear calibration graph in the range 5.0×10−3–20μM was obtained with a calibration correlation coefficient of 0.9985. The limit of detection (3sb/slope) was obtained 2.34×10−3μM. The real sample analysis was performed to determine CXB in pharmaceutical and human serum samples. The repeatability of method (n=3) were obtained 3.03%.

A novel sensor made of Antimony Doped Tin Oxide-silica composite sol on a glassy carbon electrode modified by single-walled carbon nanotubes for detection of norepinephrine

In this study, we designed a novel molecularly imprinted polymer (MIP), Antimony Doped Tin Oxide (ATO)-silica composite sol, which was made using a sol–gel method. Then a sensitive and selective imprinted electrochemical sensor was constructed with the ATO-silica composite sol on a glassy carbon electrode modified by single-walled carbon nanotubes (SWNTs). The introduction of SWNTs increased the sensitivity of the MIP sensor. The surface morphology of the MIP and MIP/SWNTs were characterized by scanning electron microscopy (SEM), and the optimal conditions for detection were determined. The oxidative peak current increased linearly with the concentration of norepinephrine in the range of 9.99×10−8M to 1.50×10−5M, as detected by cyclic voltammetry (CV), the detection limit was 3.33×10−8M (S/N=3). In addition, the proposed electrochemical sensors were successfully applied to detect the norepinephrine concentration in human blood serum samples. The recoveries of the sensors varied from 99.67% to 104.17%, indicating that the sensor has potential for the determination of norepinephrine in clinical tests. Moreover, the imprinted electrochemical sensor was used to selectively detect norepinephrine. The analytical application was conducted successfully and yielded accurate and precise results.

Ultratrace Detection of Histamine Using a Molecularly-Imprinted Polymer-Based Voltammetric Sensor.

Rapid and cost-effective analysis of histamine, in food, environmental, and diagnostics research has been of interest recently. However, for certain applications, the already-existing biological receptor-based sensing methods have usage limits in terms of stability and costs. As a result, robust and cost-effective imprinted polymeric receptors can be the best alternative. In the present work, molecularly-imprinted polymers (MIPs) for histamine were synthesized using methacrylic acid in chloroform and acetonitrile as two different porogens. The binding affinity of the MIPs with histamine was evaluated in aqueous media. MIPs synthesized in chloroform displayed better imprinting properties for histamine. We demonstrate here histamine MIPs incorporated into a carbon paste (CP) electrode as a MIP-CP electrode sensor platforms for detection of histamine. This simple sensor format allows accurate determination of histamine in the sub-nanomolar range using an electrochemical method. The sensor exhibited two distinct linear response ranges of 1 × 10−10–7 × 10−9 M and 7 × 10−9–4 × 10−7 M. The detection limit of the sensor was calculated equal to 7.4 × 10−11 M. The specificity of the proposed electrode for histamine is demonstrated by using the analogous molecules and other neurotransmitters such as serotonin, dopamine, etc. The MIP sensor was investigated with success on spiked serum samples. The easy preparation, simple procedure, and low production cost make the MIP sensor attractive for selective and sensitive detection of analytes, even in less-equipped laboratories with minimal training.

Molecular imprinting sensor based on quantum weak measurement

A new type of sensing protocol, based on a high precision metrology of quantum weak measurement, was first proposed for molecularly imprinted polymers (MIP) sensor. The feasibility, sensitivity and selectivity of weak measurement based MIP (WMMIP) sensor were experimentally demonstrated with bovine serum albumin (BSA). Weak measurement system exhibits high sensitivity to the optical phase shift corresponding to the refractive index change, which is induced by the specific capture of target protein molecules with its recognition sites. The recognition process can be finally characterized by the central wavelength shift of output spectra through weak value amplification. In our experiment, we prepared BSA@MIP with modified reversed-phase microemulsion method, and coated it on the internal surface of measuring channels assembled into the Mach-Zehnder (MZ) interferometer based optical weak measurement system. The design of this home-built optical system makes it possible to detect analyte in real time. The dynamic process of the specific adsorption and concentration response to BSA from 5×10−4 to 5×10−1μg/L was achieved with a limit of detection (LOD) of 8.01×10−12g/L. This WMMIP shows superiority in accuracy, fast response and low cost. Furthermore, real-time monitoring system can creatively promote the performance of MIP in molecular analysis.

A New Core@Shell Silica-Coated Magnetic Molecular Imprinted Nanoparticles for Selective Detection of Sunset Yellow in Food Samples

In this work, silica-coated magnetic nanoparticles were used as seed particles in the production of molecularly imprinted polymer (MIP) shells by copolymerization of ethylene glycol dimethacrylate with methacrylic acid in the presence of sunset yellow (SY) and an appropriate porogenic solvent. Thereafter, the MIP sensor was designed by covering a layer of core-shell MIP nanoparticles on a graphite-modified glassy carbon electrode (Gr/GCE). The results indicated that the MIP sensor could remarkably increase the peak current of SY and exhibited an excellent recognition capacity toward it compared with other structurally similar molecules. The detection limit of 5.5 nmol/L and two linear calibration ranges of 0.0085–1 and 1–30 μmol/L were obtained for SY determination. The proposed sensor was successfully applied for the determination of SY in several food samples without complex sample pretreatment.

Synthesis of surface molecular imprinting polymer on SiO2-coated CdTe quantum dots as sensor for selective detection of sulfadimidine

This paper demonstrates a facile method to synthesize surface molecular imprinting polymer (MIP) on SiO2-coated CdTe QDs for selective detection of sulfadimidine (SM2). The fluorescent MIP sensor was prepared using cadmium telluride quantum dots (CdTe QDs) as the material of fluorescent signal readout, sulfadimidine as template molecule, 3-aminopropyltriethoxysilane (APTES) as functional monomer and tetraethyloxysilane (TEOS) as cross-linking agent. The CdTe cores were embed in the silicon shells by a sol-gel reaction and then the molecular imprinting layers were immobilized on the surface of the SiO2-coated CdTe QDs. Under the optimized conditions, the relative fluorescent intensity weakened in a linear way with the increasing concentration of sulfadimidine in the range of 10–60μmolL−1. The practical application of the fluorescent MIP sensor was evaluated by means of analyzing sulfadimidine in the real milk samples. The recoveries were at the range of 90.3–99.6% and the relative standard deviation (RSD) ranged from 1.9 to 3.1%, which indicates the successful synthesis of the fluorescent MIP sensor. This sensor provides an alternative solution for selective determination of sulfadimidine from real milk samples.

Rapid electrochemical synthesis of molecularly imprinted polymers on functionalized multi-walled carbon nanotubes for selective recognition of sunset yellow in food samples

The monitoring of synthetic colorants in foods is very important due to their potential toxicity and pathogenicity. Therefore, we proposed a new and facile electrochemical method for the determination of sunset yellow (SY) in food samples. A highly sensitive and selective electrochemical sensor was fabricated by electropolymerization of molecularly imprinted polymer (MIP) in the presence of SY onto a functionalized multi-walled carbon nanotubes/glassy carbon electrode (f-MWCNTs/GCE) using cyclic voltammetry (CV). Scanning electron microscopy and CV were employed to characterize the fabricated sensor. The experimental parameters, such as supporting electrolyte and its pH, the monomer concentration, the number of cycles for the electropolymerization and the scan rate for the sensor preparation were optimized. The MIP sensor exhibited an excellent recognition capacity toward SY compared with other structurally similar molecules. Under the optimum operating conditions, the current response of the MIP sensor was linear to SY concentrations in the range from 0.05 to 100μM, with the detection limit of 5.0nM. Finally, the proposed electrode was successfully applied to determine SY in several food samples.

Ag/N-doped reduced graphene oxide incorporated with molecularly imprinted polymer: An advanced electrochemical sensing platform for salbutamol determination

In this work, the metallic silver and non-metallic nitrogen co-doped reduced graphene oxide (Ag-N-RGO) was first synthesized by a simple and cost-effective strategy, and then a molecularly imprinted polymer (MIP) was formed in situ at the surface of the prepared composite via electropolymerization of o-phenylenediamine in the presence of salbutamol as the template molecule. The electrochemical characterizations demonstrate that the bifunctional graphene-based composite shows improved catalytic performance than that of pristine graphene doped with one-component or none. The MIP sensor based on Ag-N-RGO owns high porous surface structure, resulting in the increased current response and enhanced recognition capacity than that of non-imprinted sensor. The outstanding performance of the developed sensor derives from the combined advantages of Ag-N-RGO with effective catalytic property and MIP with excellent selectivity. Under the optimal conditions, the electrochemical response of the developed sensor is linearly proportional to the concentration of salbutamol in the range of 0.03–20.00µmolL−1 with a low detection limit of 7 nmol L−1. The designed sensor has exhibited the multiple advantages such as low cost, simple manufacture, convenient use, excellent selectivity and good reproducibility. Finally, the proposed method has been extended for the determinations of salbutamol in human urine and pork samples, and the satisfactory recoveries between 98.9–105.3% are achieved.

A novel electrochemical sensor based on a molecularly imprinted polymer for the determination of epigallocatechin gallate.

A novel electrochemical sensor based on the molecularly imprinted polymer (MIP) was fabricated by electrochemical polymerization of β-cyclodextrins (β-CD) and epigallocatechin-gallate (EGCG) on the graphene oxide (GO) modified glassy carbon (GO/GC) electrode for the first time. The MIP/GO/GC electrode exhibits an excellent ability of specific binding of EGCG and a rapid electrochemical response, high sensitivity and selectivity for determination of EGCG. This prepared MIP sensor presents distinct advantages over conventional electrochemical methods for EGCG determination because it is a one-step preparation and the template molecule can be easily removed by cyclic voltammetry scans, and no elution reagent is required. Under the optimal experimental conditions, the linear response range for EGCG concentrations by the sensor was 3×10-8mol/L to 1×10-5mol/L and the detection limit was 8.78×10-9mol/L(S/N=3). The results demonstrate that the proposed MIP sensor can be a potential alternative for the determination of EGCG in tea samples.

Molecularly imprinted polymers on graphene oxide surface for EIS sensing of testosterone

A novel electrochemical biosensor was developed for ultrasensitive determination of testosterone from femtomolar to micromolar levels via electrochemical impedance spectroscopy (EIS) measurements. The sensor features a nanosized molecularly imprinted polymer (MIP) film that was electrochemically grafted on a graphene-oxide sheets modified electrode. The detection mechanism of this senor is explained via the change of the interfacial impedance that derived from the recognition of the target molecule. Due to the nanosheet structure as well as the high surface area of graphene-oxide, the sensitivity of the MIP sensor is enhanced remarkably. Under an optimized condition, a wide linear range from 1fM to 1µm (1×10−15–1×10−6molL−1) and a detection limit of 0.4fM (4.0×10–16molL−1) was obtained. This composite film presented a good selectivity over structurally similar steroid hormones, and a long term stability in room temperature for the detection of testosterone. Considering these advantages, the MIP/GO electrochemical biosensor could be a substitute of testosterone immunosensor, and may be further extended to the detection of other endogenous substances.

Molecularly imprinted electrochemical sensor based on bioinspired Au microflowers for ultra-trace cholesterol assay

A novel imprinted sensor for ultra-trace cholesterol (CHO) detection based on electropolymerized aminothiophenol (ATP) molecularly imprinted polymer (MIP) on a glassy carbon electrode (GCE) modified with dopamine@graphene (DGr) and bioinspired Au microflowers has been developed in this work. As the specific recognition element, the bioinspired Au microflowers were formed by Au nanoparticles (AuNPs) and wrapped by bionic polydopamine film (PDA) through electropolymerization method. These excellent biocompatible materials could capture the target CHO effectively. The morphology of the MIP modified electrode was characterized by scanning electron microscopy (SEM) and atomic force microscope (AFM). The hydrogen-bonding interaction between templates and monomers was characterized by ultraviolet spectroscopy. Under the optimal experimental conditions, the sensor's linear response range was between 10−18 and 10−13 M, with a detection limit of 3.3×10−19 M, which was much more sensitive than most available CHO detection methods in previously reports. Moreover, the MIP sensor exhibited high sensitivity for CHO, low interference, and good stability. The human serum samples analysis confirmed the applicability of this MIP sensor to quantitative analysis of ultra-trace CHO.

Molecularly imprinted Au-nanoparticle composite-functionalized EQCM sensor for l-serine

Here, a piezoelectric sensor to assess l-serine (L-ser) through functionalized Au nanoparticles on EQCM electrode is fabricated via molecular imprinting. Molecular imprinting, an alternative to natural molecular recognition phenomena, is a robust methodology where polymerization of monomers in the presence of a target molecule imprints structural information into resulting network polymers. Molecular imprinting is being proposed for the development of novel biorecognition techniques for human health and bioterrorism protection technologies. Here, imprinting matrix was prepared by AuNPs functionalized with 4-ATP electropolymerized on self assembled monolayer (SAM) formed by 4-amino thiophenol (4-ATP) on the surface of gold layer coated on EQCM electrode in presence of l-ser as template. Various parameters were optimized for controlling the performance of molecularly imprinted polymer (MIP)-sensor such as the number of electropolymerization cycles, mass deposited in each cycle, pH, etc. The prepared electrochemical-MIP sensor showed good enantioselectivity and was highly specific towards l-serine. In the optimal condition, the response of the MIP sensor to l-ser was linearly proportional to its concentration with limit of detection (LOD) as 0.41μM. Hence, a facile, specific and selective piezo-electrogravimmetric MIP sensor using surface-grafted specific molecular contours is developed for specific and selective uptake of l-ser in presence of various interferrants, in different kinds of matrices.

Electrosynthesis and binding properties of molecularly imprinted poly-o-phenylenediamine for selective recognition and direct electrochemical detection of myoglobin

Electrosynthesis of molecularly imprinted polymer (MIP) templated with myoglobin (Mb) and the reference non-imprinted polymer (NIP) was examined with o-phenylenediamine (o-PD) as a monomer. Mass-sensitive quartz crystal microbalance with dissipation monitoring supplied by an electrochemical module (EQCM-D) was applied to characterize and optimize MIP/NIP electrosynthesis. Mb rebinding was detected by direct electrocatalytic reduction of Mb by square wave voltammetry (SWV) or differential pulse voltammetry (DPV). The results obtained showed high specificity of polymeric antibodies to template Mb, with an imprinting factor determined as a ratio Imax(MIP)/Imax(NIP) of 2–4. The prepared MIP sensor is characterized by an apparent dissociation constant of (3.3±0.5)×10−9M and has a broad range of working concentrations of 1nM–1μМ, with the detection limit of 0.5nM (9ng/ml). Mb rebinding was examined in Mb-free diluted human serum spiked with Mb as well as in plasma samples of patients with acute myocardial infarction (AMI) and in control plasma of healthy donors in order to demonstrate the potential medical application of developed MIP sensors.

Computational design and multivariate optimization of an electrochemical metoprolol sensor based on molecular imprinting in combination with carbon nanotubes

This work describes the development of an electrochemical sensor based on a new molecularly imprinted polymer for detection of metoprolol (MTP) at ultra-trace level. The polypyrrole (PPy) was electrochemically synthesized on the tip of a pencil graphite electrode (PGE) which modified whit functionalized multi-walled carbon nanotubes (MWCNTs). The fabrication process of the sensor was characterized by cyclic voltammetry (CV) and the measurement process was carried out by differential pulse voltammetry (DPV). A computational approach was used to screening functional monomers and polymerization solvent for rational design of molecularly imprinted polymer (MIP). Based on computational results, pyrrole and water were selected as functional monomer and polymerization solvent, respectively. Several significant parameters controlling the performance of the MIP sensor were examined and optimized using multivariate optimization methods such as Plackett–Burman design (PBD) and central composite design (CCD). Under the selected optimal conditions, MIP sensor was showed a linear range from 0.06 to 490 μmol L−1 MTP, a limit of detection of 2.88 nmol L−1, a highly reproducible response (RSD 3.9%) and a good selectivity in the presence of structurally related molecules. Furthermore, the applicability of the method was successfully tested with determination of MTP in real samples (tablet, and serum).