Monolithic Molecularly Imprinted Polymer Research Articles

Colorimetric Sensing of Amoxicillin Facilitated by Molecularly Imprinted Polymers.

The scope of the presented research orientates itself towards the development of a Molecularly Imprinted Polymer (MIP)-based dye displacement assay for the colorimetric detection of the antibiotic amoxicillin in aqueous medium. With this in mind, the initial development of an MIP capable of such a task sets focus on monolithic bulk polymerization to assess monomer/crosslinker combinations that have potential towards the binding of amoxicillin. The best performing composition (based on specificity and binding capacity) is utilized in the synthesis of MIP particles by emulsion polymerization, yielding particles that prove to be more homogenous in size and morphology compared to that of the crushed monolithic MIP, which is an essential trait when it comes to the accuracy of the resulting assay. The specificity and selectivity of the emulsion MIP proceeds to be highlighted, demonstrating a higher affinity towards amoxicillin compared to other compounds of the aminopenicillin class (ampicillin and cloxacillin). Conversion of the polymeric receptor is then undertaken, identifying a suitable dye for the displacement assay by means of binding experiments with malachite green, crystal violet, and mordant orange. Once identified, the optimal dye is then loaded onto the synthetic receptor, and the displaceability of the dye deduced by means of a dose response experiment. Alongside the sensitivity, the selectivity of the assay is scrutinized against cloxacillin and ampicillin. Yielding a dye displacement assay that can be used (semi-)quantitatively in a rapid manner.

Simplified miniaturized analytical set-up based on molecularly imprinted polymer directly coupled to UV detection for the determination of benzoylecgonine in urine

A simple, selective, and sensitive method involving a miniaturized solid phase extraction step based on a monolithic molecularly imprinted polymer (MIP) directly coupled on-line to UV detection was developed for the determination of benzoylecgonine (BZE) in complex biological samples. Monolithic MIPs were prepared into 100 μm internal diameter fused-silica capillaries either by thermal or photopolymerization. While leading to similar selectivities with respect to BZE, photopolymerization has made it possible to produce monoliths of different lengths that can be adapted to the targeted miniaturized application. The homogeneous morphology of these monolithic MIPs was evaluated by scanning electron microscopy prior to measuring their permeability. Their selectivity was evaluated leading to imprinting factors of 2.7 ± 0.1 for BZE and 4.0 ± 0.6 for cocaine (selected as template for the MIP synthesis) with polymers resulting from three independent syntheses, showing both the high selectivity of the MIPs and the reproducibility of their synthesis. After selecting the appropriate capillary length and the set-up configuration and optimizing the extraction protocol to promote selectivity, the extraction of BZE present in human urine samples spiked at 150, 250, and 500 ng mL−1 was successfully carried out on the monolithic MIP and coupled directly on-line with UV detection. The very clean-baseline of the resulting chromatograms revealing only the peak of interest for BZE illustrated the high selectivity brought by the monolithic MIP. Limits of detection and quantification of 56.4 ng mL−1 and 188.0 ng mL−1 were achieved in urine samples, respectively. It is therefore possible to achieve analytical threshold in accordance with the legislation on BZE detection in urine without the need for an additional chromatographic separation.

Improving imprinting effect by reducing sites embedding: Selective extraction of 1,2,3,4,6-penta-O-galloyl-β-d-glucose from Paeonia lactiflora Pall by hydrophilic molecularly imprinted polymers based on macromonomer and metal ion pivot

1,2,3,4,6-Penta-O-galloyl-β-d-glucose (β-PGG) is one of active component of polyphenol tannic acid in the rhizome of radix paeoniae alba, and isolating and purifying β-PGG from crude extract of Paeonia lactiflora Pall is rather challenge work. In this paper, to reduce the embedding of imprinted sites and increase the binding capacity, β-PGG imprinted monoliths were synthesized using a strategy of combination of hydrophilic macromonomer with metal ions as pivot. With a small side chain of oligoethylene glycol, oligo (ethyleneglycol) methyl ether methacrylate (OEG) was chosen as the hydrophilic macromonomer. 4-Vinylpyridine (4-VP) and ethyleneglycol dimethacrylate was used as functional monomer and crosslinker, respectively, and Ni2+ was adopted as metallic pivot. Polymerization parameters, including the ratio of functional monomer/template, ratios of 4-VP to Ni2+, and ratios of OEG to 4-VP on affinity of the resulting molecularly imprinted polymer (MIP) were systematically investigated. The structure and morphology of the obtained monolithic MIP was studied by field emission scanning electron microscopy and multipoint BET measurement. The greatest imprinting factor can be achieved to 68, which gave rise to excellent selectivity of the resulting MIP. When using the MIP as SPE absorbent, the mean recoveries for β-PGG were 74.1% with purity of 98.35%. The results demonstrated that the combination of metal ion pivot with hydrophilic macromonomer is effective approach to the balance of rigidity of imprinting cavities and polymer flexibility and increase the selectivity of the resulting MIP.

Quantitative Analysis of Artificial Sweeteners by Capillary Electrophoresis with a Dual‐Capillary Design of Molecularly Imprinted Solid‐Phase Extractor

A novel coupling system of capillary electrophoresis (CE) and monolithic molecularly imprinted polymer (MIP) was developed for selective and sensitive determination of sweeteners; sucrose, sucralose, and aspartame, based on an in‐column and open‐tube molecularly imprinted solid‐phase extraction (MISPE) concentrator. The MISPE was fabricated by coating a short layer of MIP material (about 3 mm long) directly at the inlet end of the inner wall of capillaries under the irradiation of light emitting diode (LED). Compared with the conventional methods using hydrodynamic injection by MISPE fiber, the MISPE concentrator provides increase in sensitivity without significant loss of separation efficiency. In this work, LED‐induced in‐multiple capillary MISPE was used for extraction and determination of artificial sweeteners, sucrose, sucralose, and aspartame, from beverage samples. The results of MISPE showed good extraction ability with the enrichment ratios of >150 for sucrose and sucralose, and of >200 for aspartame with acceptable analytical performance. The reproducibility of on‐line MISPE concentrator was 1.6% for sucralose and 2.7% for aspartame under the same fixed set of experimental conditions. The developed multiple MISPE system has been successfully adapted for practical application for commercial soda drink samples.

Rapid Preparation of Monolithic Molecular Imprinted Polymer Fiber for Solid Phase Microextraction by Microwave Irradiation

AbstractIn this paper, a simple, fast and in situ polymerization strategy to prepare monolithic molecularly imprinted polymer (MIP) fibers for solid phase microextraction (SPME) is developed using silica capillaries as molds. With the help of microwave irradiation, polymerization was carried out in 5.5 min using olivetol as a template molecular, α‐methacrylic acid (MAA) as a functional monomer and ethylene dimethacrylate (EDMA) as a crosslinker, toluene and dodecanol as the binary porgens. The resulted MIP fibers were finally obtained after silica being etched away with a controlled length, and subsequently characterized by scanning electron microscope (SEM) and Fourier transform infrared absorption spectroscopy (FT‐IR). Under the optimal extraction conditions, a simple method based on the coupling of MIP SPME with high performance liquid chromatography (HPLC) was used for the selective determination of the model mixtures of olivetol, phenol and m‐toluidine in lake water and wheat bran samples. The recoveries of olivetol, phenol and m‐toluidine for both samples were in the range of 87.3‐93.6%, 21.4‐27.2%, 18.9‐24.8% at three spiked levels, respectively, demonstrating that higher extraction and the specific absorption occurred between the template molecule and the prepared MIP fiber.

A novel method to prepare monolithic molecular imprinted polymer fiber for solid‐phase microextraction by microwave irradiation†

In this paper, a new approach to prepare monolithic molecularly imprinted polymer (MIP) fibers for solid-phase microextraction is proposed with the help of microwave irradiation. Imprinting polymerization was carried out within silica capillaries in 4.5 min, using dimethyl phthalate (DMP) as a template molecular, α-methacrylic acid as a functional monomer and ethylene dimethacrylate as a crosslinker, acetonitrile as the porogenic solvent. The synthesis was optimized by varying the ratio of template/monomer and different volume of porogen. The resulted MIP fibers were obtained after silica being etched away with a controlled length of 1 cm, and subsequently characterized by SEM. In order to increase the selective extraction of DMP, factors affecting the extraction including extraction time, salt concentration, desorption time, and desorption solvents were investigated for solid-phase microextraction procedures in detail. The selectivity coefficients, defined as the extraction amount ratio of MIP to its nonimprinting fiber, were 5.6, 2.6, and 1.4 for DMP and its counterpart including dibutyl phthalate and di-n-octylo-phthalate, respectively. The resulted fibers were also applied to detect DMP, dibutyl phthalate, and di-n-octylo-phthalate in bottled beverage samples coupled to HPLC and resulted in relative recoveries of up to 73.8-98.5%, respectively.

Microwave-assisted preparation of monolithic molecularly imprinted polymeric fibers for solid phase microextraction

In this work, a novel microwave-assisted method was developed for fast and batch fabrication of monolithic molecularly imprinted polymer (MIP) fibers. It was based on in situ polymerization in a flexible capillary mold under microwave irradiation. The proposed method greatly shortened the preparation time (about 20-fold) in comparison with the conventional heating. The model template, bisphenol A (BPA) imprinted MIP fiber, was prepared and used for solid phase microextraction (SPME) prior to high performance liquid chromatography (HPLC) determination of BPA and its analogues, i.e., diethylstilbestrol (DES) and hexestrol (HEX). Under the established optimum conditions, the limits of detection for BPA, DES and HEX were 2.0 ng mL(-1), 5.1 ng mL(-1), and 3.3 ng mL(-1), respectively. The fiber-to-fiber extraction (n = 5) was reproducible with the relative standard deviation in the range of 6.6-9.5%. The MIP fiber was used for selective extraction of BPA, DES and HEX in tap water, sewage and urine samples, and the relative recoveries for MIP-SPME-HPLC analysis of BPA, DES and HEX ranged from 82.5% to 103.8%. The advantages provided by this microwave-assisted method will make it a useful tool for preparation of MIP fibers with good SPME performance.

Preparation and characterization of grafted imprinted monolith for capillary electrochromatography

In this paper, a molecularly imprinted polymer (MIP) coating grafted to a trimethylolpropane trimethacrylate (TRIM) core material for CEC was reported. The core monolith was prepared with a solution of 20% (w/w) TRIM in a mixture of porogen and a polymerization precursor, which can generate a stable electroosmotic flow due to the formation of ionizable groups after postpolymerization hydrolization. Graft polymerization took place on the resultant TRIM monolith with a mixture of template, methacrylic acid, and ethylene glycol dimethacrylate. Strong recognition ability (selectivity factor was 5.83) for S-amlodipine and resolution of enatiomers separation (up to 7.99) were obtained on the resulting grafted imprinted monolith in CEC mode. The influence of CEC conditions on chiral separation, including the composition of mobile phase, pH value, and the operating voltages was studied. These results suggest that the method of grafted polymerization reported here allows a rapid development of MIP monolith once core materials with desired properties are available, and is a good alternative to prepare CEC-based monolithic MIPs.

SPR Detection of Dopamine Using Cathodically Electropolymerized, Molecularly Imprinted Poly‐p‐aminostyrene Thin Films

AbstractA molecularly imprinted polymer (MIP) film for dopamine (DP) sensing is fabricated from cathodically electrodeposited p‐aminostyrene (PAS) on electrode surfaces in a surface plasmon resonance (SPR) spectroscopy setup. The monomer is more commonly used in monolithic MIP free‐radical bulk polymerizations. The film growth and rebinding of DP are monitored by electrochemical‐SPR (EC‐SPR) spectroscopy. UV–Vis, IR spectroscopy, XPS, AFM, and electrochemistry methods are used to characterize the film. High selectivity against analogous analytes and up to picomolar detection of DP is demonstrated. The reusability of the sensor is also established. Theoretical modeling studies with AM1 calculations predict H‐bonding in a stable prepolymerization complex in solution prior to MIP film formation.

Synthesis of monolithic HPLC stationary phase with self‐assembled molecular recognition sites for 4‐aminophenol

AbstractA molecularly imprinted polymer (MIP) monolith for selective recognition of 4‐aminophenol (4‐AMP) was prepared by in situ polymerization technique as high‐performance liquid chromatography (HPLC) stationary phase. For this purpose, several 4‐AMP imprinted monoliths were synthesized by using only methacrylic acid (MAA), acrylamide (AAM), or isobornyl methacrylate (IBMA) in the presence of high amount of crosslinker, ethylene glycol dimethacrylate (EDMA), and these polymeric monolith columns were connected to HPLC to evaluate their separation capabilities. By selection of appropriate functional monomer and optimization of polymerization conditions, MAA‐based monolithic MIP showed good flow through properties, high selectivity to the templated molecule, and high resolution in the separation of paracetamol and its main impurity, 4‐AMP. Besides, effective binding site density and dissociation constant of this monolith were estimated by using frontal chromatography and found as 7.95 μmol/g and 1.06 mM, respectively. Surface area of the same monolith was found as 23.48 m2/g from multipoint BET analysis. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011

Preparation and evaluation of a monolithic molecularly imprinted polymer for the chiral separation of neurotransmitters and their analogues by capillary electrochromatography

A monolithic molecularly imprinted polymer (MIP) column was prepared as the stationary phase for the capillary electrochromatographic (CEC) separation of a group of structurally related compounds including dopamine (DA), (±)-epinephrine (EP), (−)-isoproterenol (ISO), (±)-norepinephrine (NE), (±)-octopamine (OCT), and (±)-synephrine (SYN). Here, (−)-NE was used as the template. Either methacrylic acid (MAA) or itaconic acid (IA) together with a mixture of ethylene glycol dimethacrylate (EDMA) and α,α′-azobis(isobutyronitrile) (AIBN) in N, N-dimethylformamide (DMF) was introduced into a pre-treated, silanised, fused-silica capillary by a thermal non-covalent polymerisation procedure. Optimised conditions for the polymerisation reaction were assessed by the separation efficiency of the template. Both the template/monomer/cross linker molar ratio and the compositions of the functional monomer, cross-linker, and porogen affected polymerisation. The optimum in situ polymerisation reaction was performed at 65 °C for 17 min. By varying CEC parameters like eluent composition and pH, we observed that the addition of SDS to the eluent clearly improved the CEC separations. With a mobile phase of citrate buffer (10 mM, pH 3)/SDS (40 mM)/acetonitrile (2/2/1, v/v/v) solution and an applied voltage of 10 kV, the six related structures of the template and their enantiomeric mixtures were satisfactorily separated at 30 °C.

Enrofloxacin‐imprinted monolithic columns synthesized using reversible addition‐fragmentation chain transfer polymerization

Molecularly imprinted monolithic columns for selective separation of enrofloxacin were prepared by Reversible Addition-Fragmentation Chain Transfer (RAFT)-mediated radical polymerization. Different ratios of initiation system were used in the synthesis. The structures of the monoliths were characterized to study the relationship between the synthetic conditions and morphology of the monolithic material. The separation performance of the monoliths was evaluated by liquid chromatography. Under optimized synthetic conditions, a monolithic molecularly imprinted polymer (MIP) with high selectivity and improved column efficiency was obtained. The research has shown that RAFT polymerization provides more adjustable conditions for making monolithic materials with different morphologies. The results also demonstrated that homogeneous macro-pore size distribution and large specific surface area are the key factors providing good separation ability and column efficiency for MIP monolithic structures.

Characteristic and Molecular Recognition Mechanism of Theophylline Monolithic Molecularly Imprinted Polymer

A monolithic molecularly imprinted polymer (MIP) with specific recognition ability for theophylline was prepared by in‐situ therm polymerization, using acrylamide as a functional monomer, ethylene glycol dimethacrylate as a cross‐linking agent, toluene and dodecanol as porogenic solvents and 2,2′‐azobisisobutyronitrile as initiator. Scanning electron microscopy and an accelerated surface area and porosimetry system were used to identify the structural features of the MIP. The results show that the large through‐pore structure allows mobile phase to flow through the MIP column with a low back pressure, and the other pores lead to the molecular recognition. Some chromatographic conditions such as the composition of the mobile phase, flow rate, and temperature were characterized and illustrated by a homologous series of xanthine derivatives, theophylline and caffeine. Effects of molecular recognition were also discussed and the possible recognition mechanisms were hydrogen bonding and hydrophobic interactions between the theophylline molecule and the MIP.

Mechanism of molecular recognition on molecular imprinted monolith by capillary electrochromatography

The recognition mechanism of molecularly imprinted polymer (MIP) in capillary electrochromatography (CEC) is complicated since it possesses a hybrid process, which comprises the features of chromatographic retention, electrophoretic migration and molecular imprinting. For an understanding of the molecular recognition of MIP in CEC, a monolithic MIP in a capillary with 1,1′-binaphthyl-2,2′-diamine (BNA) imprinting was prepared by in situ copolymerization of imprinted molecule, methacrylic acid and ethylene glycol dimethacrylate in porogenic solvent, a mixture of toluene-isooctane. Strong recognition ability and high column performance (theory plates was 43,000 plates/m) of BNA were achieved on this monolithic MIP in CEC mode. In addition, BNA and its structural analogue, 1,1′-bi-2, 2′-naphthol, differing in functional groups, were used as model compounds to study imprinting effect on the resultant BNA-imprinted monolithic column, a reference column without imprinting of BNA and a open capillary. The effects of organic modifier concentration, pH value of buffer, salt concentration of buffer and column temperature on the retention and recognition of two compounds were investigated. The results showed that the molecular recognition on MIP monolith in CEC mode mainly derived from imprinting cavities on BNA-imprinted polymer other than chromatographic retention and electrophoretic migration.

Computational Fluid Dynamics Models of Molecularly Imprinted Materials in Microfluidic Channels

AbstractCurrent research will lead to rapid-prototyping of chemical sensors that utilize microfabricated molecularly imprinted (MI) materials. CFD/CAD software may be used to model flow and chemical binding properties of MI materials in microfluidic channels. Use of this type of software expedites results when changes in properties are made. The surface concentration of bound analyte on a monolithic molecularly imprinted polymer (MIP) within microfluidic channels can be modeled using its experimental binding kinetics. The time necessary to reach a detection limit is calculated and optimized as a function of flow parameters. In this report, we discuss the unique issues associated with the modeling of chemical sensors that utilize MI materials.