Molecularly Imprinted Polymer Nanoparticles Research Articles

Fabricating Ultrathin Imprinting Layer for Fast Capture of Valsartan via a Metal Affinity-Oriented Surface Imprinting Method.

Rapid separation and enrichment of targets in biological matrixes are of significant interest in multiple life sciences disciplines. Molecularly imprinted polymers (MIPs) have vital applications in extraction and sample cleanup owing to their excellent specificity and selectivity. However, the low mass transfer rate, caused by the heterogeneity of imprinted cavities in polymer networks and strong driving forces, significantly limits its application in high-throughput analysis. Herein, one novel metal affinity-oriented surface imprinting method was proposed to fabricate an MIP with an ultrathin imprinting layer. MIPs were prepared by immobilized template molecules on magnetic nanoparticles (NPs) with metal ions as bridges via coordination, and then polymerization was done. Under the optimized conditions, the thickness of the imprinting layer was merely 1 nm, and the adsorption toward VAL well matched the Langmuir model. Moreover, it took just 5 min to achieve adsorption equilibrium significantly faster than other reported MIPs toward VAL. Adsorption capacity still can reach 25.3 mg/g ascribed to the high imprinting efficiency of the method (the imprinting factor was as high as 5). All evidence proved that recognition sites were all external cavities and were evenly distributed on the surface of the NPs. The obtained MIP NPs exhibited excellent selectivity and specificity toward VAL, with good dispersibility and stability. Coupled with high-performance liquid chromatography, it was successfully used as a dispersed solid phase extraction material to determine VAL in serum. Average recoveries are over 90.0% with relative standard deviations less than 2.14% at three spiked levels (n = 3). All evidence testified that the MIPs fabricated with the proposed method showed a fast trans mass rate and a large rebinding capacity. The method can potentially use high-throughput separation and enrichment of target molecules in batch samples to meet practical applications.

Intrinsic tenase blood biomarker imprinted polymer-aptasensor with carbon nanohorn and gold nano-urchin construct for primitive-phase diagnosis of haemophilia B

The selective biomimetic aptasensor for blood coagulation factor IX protein (FIX) detection was developed using an interdigitated electrode with an Archimedean spiral pattern. In contrast to conventional molecularly imprinted polymer (MIP) techniques, aptamer was employed as a macromonomer to accelerate double binding affinity. To preserve the aptamer profile in its protein-binding orientation, FIX protein and thiol-modified RNA aptamers were complexed prior to MIP fabrication. The immobilized aptamer-FIX complex was surrounded by a polymer generated by the electropolymerization of 3-thiophene acetic acid (3TAA). Subsequent to FIX protein removal, leaves imprinted cavities facilitate selective FIX protein detection in conjunction with the affinity of embedded aptamer affinity. The Archimedean IDE surface was functionalized with carbon nanohorn (CNH) and gold nanourchin (GNU) to increase the imprinting ratios and sensor sensitivity. The developed FIX-aptasensor shows a detection limit of 0.06 fM, which is 660-fold higher than aptamer-embedded MIP nanoparticles. Moreover, the sensor exhibited greater selectivity for FIX, discriminating IgG and thrombin. As a preliminary study for clinical use, the sensor was used to analyze human serum without target spiking and detected FIX-protein with a relative standard deviation of 9.18%. It was ascertained that the sensor maintained 85% sustained performance for a duration of five weeks.

Molecularly imprinted polymer-based SERS sensing of transferrin in human serum.

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.

Modulation of EGFR Activity by Molecularly Imprinted Polymer Nanoparticles Targeting Intracellular Epitopes.

In recent years, molecularly imprinted polymer nanoparticles (nanoMIPs) have proven to be an attractive alternative to antibodies in diagnostic and therapeutic applications. However, several key questions remain: how suitable are intracellular epitopes as targets for nanoMIP binding? And to what extent can protein function be modulated via targeting specific epitopes? To investigate this, three extracellular and three intracellular epitopes of epidermal growth factor receptor (EGFR) were used as templates for the synthesis of nanoMIPs which were then used to treat cancer cells with different expression levels of EGFR. It was observed that nanoMIPs imprinted with epitopes from the intracellular kinase domain and the extracellular ligand binding domain of EGFR caused cells to form large foci of EGFR sequestered away from the cell surface, caused a reduction in autophosphorylation, and demonstrated effects on cell viability. Collectively, this suggests that intracellular domain-targeting nanoMIPs can be a potential new tool for cancer therapy.

Development of Molecularly Imprinted Polymer Nanoparticles with High Affinity and Its Application to Electrochemical Biosensors

Molecularly imprinted polymers (MIPs) have the potentials to be low-cost and stable alternatives to natural receptors such as enzymes and antibodies for biosensors. In our group, we have been developing enzyme-/antibody-free electrochemical biosensors with the MIP-coated electrodes [1,2]. However, the conventional polymerization methods for MIPs have the limitations such as their heterogeneities that reduce high binding affinity sites and the presence of residual templated molecules, which are detrimental to biomolecular recognition. To address these issues, we have synthesized molecularly imprinted polymer nanoparticles (nano-MIPs) with virtually free of heterogeneous templates and higher affinity for target biomolecules by using a solid-phase approach synthesis method [3]. In this study, we have focused on the biomarkers such as human serum albumin (HSA) and glycated albumin (GA) for diabetes and then synthesized the redox-labeled HSA-templated nano-MIPs (HNMs) and GA-templated nano-MIPs (GNMs) for the electrochemical biosensor (Figure 1). The fundamental characteristics of HNMs and GNMs such as chemical composition, particle size, and binding affinity have been evaluated by using proton nuclear magnetic resonance (1H NMR), dynamic light scattering (DLS), atomic force microscopy (AFM), cyclic voltammetry (CV), isothermal titration calorimetry (ITC), and surface plasmon resonance (SPR).References Kajisa, T.; Sakata, T. ACS Appl. Mater. Interfaces 2018,10, 34983–34990.Sakata, T.; Nishitani, S.; Kajisa, T. RSC Advances 2020, 10, 16999–17013.Canfarotta, F. et al. Nat. Protoc. 2016, 3, 443-455. Figure 1

A Computationally Assisted Approach for Designing Wearable Biosensors toward Non-Invasive Personalized Molecular Analysis.

Wearable sweat sensors have the potential to revolutionize precision medicine as they can non-invasively collect molecular information closely associated with an individual's health status. However, the majority of clinically relevant biomarkers cannot be continuously detected in situ using existing wearable approaches. Molecularly imprinted polymers (MIPs) are a promising candidate to address this challenge but haven't yet gained widespread use due to their complex design and optimization process yielding variable selectivity. Here, QuantumDock is introduced, an automated computational framework for universal MIP development toward wearable applications. QuantumDock utilizes density functional theory to probe molecular interactions between monomers and the target/interferent molecules to optimize selectivity, a fundamentally limiting factor for MIP development toward wearable sensing. A molecular docking approach is employed to explore a wide range of known and unknown monomers, and to identify the optimal monomer/cross-linker choice for subsequent MIP fabrication. Using an essential amino acid phenylalanine as the exemplar, experimental validation of QuantumDock is performed successfully using solution-synthesized MIP nanoparticles coupled with ultraviolet-visible spectroscopy. Moreover, a QuantumDock-optimized graphene-based wearable device is designed that can perform autonomous sweat induction, sampling, and sensing. For the first time, wearable non-invasive phenylalanine monitoring is demonstrated in human subjects toward personalized healthcare applications.

Development of Molecularly Imprinted Polymer Nanoparticles with High Affinity and Its Application to Electrochemical Biosensors

In this study, redox-labeled molecularly imprinted polymer nanoparticles (nano-MIPs) were synthesized using a solid-phase approach, templated with biomarkers for diabetes such as human serum albumin (HSA). The purpose of this research was to develop enzyme-/antibody-free electrochemical biosensors with the nano-MIP-coated Au electrodes. The synthesized HSA–nano-MIP (HNM) was analyzed for its chemical composition, size, affinity, and electrochemical property, and was tethered on gold via a coupling chemistry. The results of cyclic voltammetry analysis revealed that electron transfer occurred on the HNM-immobilized Au electrode through physical displacement of the redox centers within HNM, which hopped from one redox center to an adjacent redox center, a process known as bounded diffusion. In this paper, we present a promising approach to developing sensitive and selective electrochemical biosensors for diabetes detection.

Biodegradable and Sustainable Synthetic Antibodies-A Perspective.

Molecular imprinting technology has been around for almost a century, and we have witnessed dramatic advancements in the overall design and production of molecularly imprinted polymers (MIPs), particularly in terms of possible formats of the final products when it comes to truly resembling antibody substitutes, i.e., MIP nanoparticles (MIP NPs). Nonetheless, the overall technology appears to struggle to keep up with the current global sustainability efforts, as recently elucidated in the latest comprehensive reviews, which introduced the "GREENIFICATION" concept. In this review, we will try to elucidate if these advancements in MIP nanotechnology have indeed resulted in a sustainability amelioration. We will do so by discussing the general production and purification strategies for MIP NPs, specifically from a sustainability and biodegradation perspective, also considering the final intended application and ultimate waste management.

Molecularly Imprinted Nanoparticle Ensembles for Rapidly Identifying S. epidermidis

Staphylococcus epidermidis (S. epidermidis) belongs to methicillin-resistant bacteria strains that cause severe disease in humans. Herein, molecularly imprinted polymer (MIP) nanoparticles resulting from solid-phase synthesis on entire cells were employed as a sensing material to identify the species. MIP nanoparticles revealed spherical shapes with diameters of approximately 70 nm to 200 nm in scanning electron microscopy (SEM), which atomic force microscopy (AFM) confirmed. The interaction between nanoparticles and bacteria was assessed using height image analysis in AFM. Selective binding between MIP nanoparticles and S. epidermidis leads to uneven surfaces on bacteria. The surface roughness of S. epidermidis cells was increased to approximately 6.3 ± 1.2 nm after binding to MIP nanoparticles from around 1 nm in the case of native cells. This binding behavior is selective: when exposing Escherichia coli and Bacillus subtilis to the same MIP nanoparticle solutions, one cannot observe binding. Fluorescence microscopy confirms both sensitivity and selectivity. Hence, the developed MIP nanoparticles are a promising approach to identify (pathogenic) bacteria species.

Computational Assisted-Molecular Imprinted Polymer Design for Magnetic Solid Phase Extraction of Pinostrobin from Krachai

The Covid-19 pandemic is driving the use of herbal extracts to treat early stages of Covid-19 symptoms, particularly in light of the increased demand for Krachai (Boesenbergia rotunda (L.) Mansf.) with significant pharmacological properties. However, the relevance of establishing extract methods is still necessary for Krachai standardization at an industrial level for continued industrial development of food and health products. The purpose of this work was to develop a unique solid phase extraction with particular recognition produced by imprinting technology on the suface of Fe3O4 nanoparticles that may enable selective absorption of pinostrobin, an active ingredient in Krachai. Pre-polymerization procedure of molecularly imprinted polymer (MIP) nanoparticles specific to pinostrobin was critical to computational aided-design MIP nanoparticles in this preliminary study. The molecular modeling interactions between two mixed functional monomers, methacrylic acid and vinylpyridine, in the presence of pinostrobin, a printed molecule were used by Hyperchem 7.5 software package. The complex was built and simulated in various ratios of template and functional monomer conformations in order to geometrically optimize it to the lowest energy state in the gas phase. The estimated free binding energies of each conformation were calculated using the semi-empirical PM3 simulation method. The results showed that interactions with the ratio of 1:2:2 (pinostrobin: methacrylic acid: vinylpyridine) had the maximized free binding energy when compared to interactions with other ratios. Additionally, the FT-IR approach was

Rapid Conductometric Detection of SARS-CoV-2 Proteins and Its Variants Using Molecularly Imprinted Polymer Nanoparticles.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biosensors have captured more attention than the conventional methodologies for SARS-CoV-2 detection due to having cost-effective platforms and fast detection. However, these reported SARS-CoV-2 biosensors suffer from drawbacks including issues in detection sensitivity, degradation of biomaterials on the sensor's surface, and incapability to reuse the biosensors. To overcome these shortcomings, molecularly imprinted polymer nanoparticles (nanoMIPs) incorporated conductometric biosensor for highly accurate, rapid, and selective detection of two model SARS-CoV-2 proteins: (i) receptor binding domain (RBD) of the spike (S) glycoprotein and (ii) full length trimeric spike protein are introduced. In addition, these biosensors successfully responded to several other SARS-CoV-2 RBD spike protein variants including Alpha, Beta, Gamma, and Delta. Our conductometric biosensor selectively detects the two model proteins and SARS-CoV-2 RBD spike protein variant samples in real-time with sensitivity to a detection limit of 7 pg mL-1 within 10 min of sample incubation. A battery-free, wireless near-field communication (NFC) interface is incorporated with the biosensor for fast and contactless detection of SARS-CoV-2 variants. The smartphone enabled real-time detection and on-screen rapid result for SARS-CoV-2 variants can curve the outbreak due to its ability to alert the user to infection in real time.

Synthesis of Molecularly Imprinted Polymer Nanoparticles for SARS-CoV-2 Virus Detection Using Surface Plasmon Resonance

COVID-19 caused by a SARS-CoV-2 infection was first reported from Wuhan, China, and later recognized as a pandemic on March 11, 2020, by the World Health Organization (WHO). Gold standard nucleic acid and molecular-based testing have largely satisfied the requirements of early diagnosis and management of this infectious disease; however, these techniques are expensive and not readily available for point-of-care (POC) applications. The COVID-19 pandemic of the 21st century has emphasized that medicine is in dire need of advanced, rapid, and cheap diagnostic tools. Herein, we report on molecularly imprinted polymer nanoparticles (MIP-NPs/nanoMIPs) as plastic antibodies for the specific detection of SARS-CoV-2 by employing a surface plasmon resonance (SPR) sensor. High-affinity MIP-NPs directed against SARS-CoV-2 were manufactured using a solid-phase imprinting method. The MIP-NPs were then characterized using dynamic light scattering (DLS) and atomic force microscopy (AFM) prior to their incorporation into a label-free portable SPR device. Detection of SARS-CoV-2 was studied within a range of 104–106 PFU mL−1. The MIP-NPs demonstrated good binding affinity (KD = 0.12 pM) and selectivity toward SARS-CoV-2. The AFM, cyclic voltammetry, and square-wave voltammetry studies revealed the successful stepwise preparation of the sensor. A cross-reactivity test confirmed the specificity of the sensor. For the first time, this study demonstrates the potential of molecular imprinting technology in conjunction with miniaturized SPR devices for the detection of SARS-CoV-2 particles with high-affinity and specificity. Such sensors could help monitor and manage the risks related to virus contamination and infections also beyond the current pandemic.

Assessing the In Vivo Biocompatibility of Molecularly Imprinted Polymer Nanoparticles.

Molecularly imprinted polymer nanoparticles (nanoMIPs) are high affinity synthetic receptors which show promise as imaging and therapeutic agents. Comprehensive analysis of the in vivo behaviour of nanoMIPs must be performed before they can be considered for clinical applications. This work reports the solid-phase synthesis of nanoMIPs and an investigation of their biodistribution, clearance and cytotoxicity in a rat model following both intravenous and oral administration. These nanoMIPs were found in each harvested tissue type, including brain tissue, implying their ability to cross the blood-brain barrier. The nanoMIPs were cleared from the body via both faeces and urine. Furthermore, we describe an immunogenicity study in mice, demonstrating that nanoMIPs specific for a cell surface protein showed moderate adjuvant properties, whilst those imprinted for a scrambled peptide showed no such behaviour. Given their ability to access all tissue types and their relatively low cytotoxicity, these results pave the way for in vivo applications of nanoMIPs.

Novel biodegradable molecularly imprinted polymer nanoparticles for drug delivery of methotrexate anti-cancer; synthesis, characterization and cellular studies.

Recently biodegradable nanoparticles are the center of attention for the development of drug delivery systems. Molecularly imprinted polymer (MIP) is an interesting candidate for designing drug nano-carriers. MIP-based nanoparticles could be used for cancer treatment and exhibited the potential to fill gaps regarding to ligand-based nanomaterials. Also, the presence of a cross-linker can play an essential role in nanoparticle stability and physicochemical properties of nanoparticles after synthesis. In this research, a biodegradable drug delivery system based on MIP nanoparticles was prepared using a biodegradable cross-linker (dimethacryloyl hydroxylamine, DMHA) for methotrexate (MTX). A hydrolysable functional group CO-O-NH-CO was added to the crosslinking agent to increase the final biodegradability of the polymer. Firstly, a biodegradable cross-linker was synthesized. Then, the non-imprinted polymers were prepared through mini-emulsion polymerization in the absence of a template; and efficient particle size distribution was determined. Finally, methotrexate was placed in imprinted polymers to achieve the desired MIP. Different types of MIPs were synthesized using different molar ratios of template, cross-linker, and functional monomer, and the optimal molar ratio was obtained at 1:4:20, respectively. HNMR successfully confirmed the chemical structure of the cross-linker. According to SEM images, nanoparticles had a spherical shape with a smooth surface. The imprinted nanoparticles showed a narrow size distribution with an average of 120nm at a high ratio of cross-linker. The drug loading and entrapment efficiency were 6.4% and 92%, respectively. The biodegradability studies indicated that the nanoparticles prepared by DMHA had a more degradability rate than ethylene glycol dimethacrylate as a conventional cross-linker. Also, the polymer degradation rate was higher in alkaline environments. Release studies in physiological and alkaline buffer showed an initial burst release of a quarter of loaded MTX during the day and a 70% release during a week. The Korsmeyer-Peppas model described the release pattern. The cytotoxicity of MTX loaded in nanoparticles was studied on the MCF-7 cell line, and the IC50 was 3.54μg/ml. It was demonstrated that nanoparticles prepared by DMHA have the potential to be used as biodegradable drug carriers for anticancer delivery. Synthesis schema of molecular imprinting of methotrexate in biodegradable polymer based on dimethacryloyl hydroxylamine cross-linker, for use as nanocarrier anticancer delivery to breast tumor.

Effect of Recombinant Antibodies and MIP Nanoparticles on the Electrical Behavior of Impedimetric Biorecognition Surfaces for SARS-CoV-2 Spike Glycoprotein: A Short Report

Electrochemical immunosensors are often described as innovative strategies to tackle urgent epidemiological needs, such as the detection of SARS-CoV-2 main biomarker, the spike glycoprotein. Nevertheless, there is a great variety of receptors, especially recombinant antibodies, that can be used to develop these biosensing platforms, and very few reports compare their suitability in analytical device design and their sensing performances. Therefore, this short report targeted a brief and straightforward investigation of the performance of different impedimetric biorecognition surfaces (BioS) for SARS-CoV-2, which were crafted from three commonly reported recombinant antibodies and molecularly-imprinted polymer (MIP) nanoparticles (nanoMIP). The selected NanoMIP were chosen due to their reported selectivity to the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein. Results showed that the surface modification protocol based on MUDA and crosslinking with EDC/NHS was successful for the anchoring of each tested receptor, as the semicircle diameter of the Nyquist plots of EIS increased upon each modification, which suggests the increase of Rct due to the binding of dielectric materials on the conductive surface. Furthermore, the type of monoclonal antibody used to craft the BioS and the artificial receptors led to very distinct responses, being the RBD5305 and the NanoMIP-based BioS the ones that showcased the highest increment of signal in the conditions herein reported, which suggests their adequacy in the development of impedimetric immunosensors for SARS-CoV-2 spike glycoprotein.

An ultra-sensitive and highly selective impedimetric sensor for vitamin D measurement based on a novel imprinted polymer synthesized utilizing template-derived functional monomer

A novel vitamin D3-imprinted (VD)-polymer was synthesized utilizing a functional monomer derived from vitamin D3. Acryloyl chloride reacted with VD leading to a functional monomer capable of interaction with VD during the molecularly imprinted polymer (MIP) synthesis step. Vitamin D3-derived functional monomer and divinylbenzene were copolymerized in the presence of vitamin D3 in order to create a new MIP, holding VD selective cavities, after template (VD) removal from the polymer. The MIP nanoparticles were used for the modification of a carbon paste electrode to fabricate VD selective sensor. The charge transfer resistance of Fe(CN)63-/Fe(CN)64−couple for the MIP-modified electrode increased significantly in the presence of VD; whereas, the non-imprinted polymer (NIP)-CPE electrode was not affected by VD, suggesting well acting of recognition sites of the MIP nanoparticles, incorporated into the electrode. The sensing mechanism was attributed to a gate effect principle. Interring of VD molecules to the selective sites of the MIP nanoparticles, existing on the electrode surface, makes the MIP particles swell and this leads to blocking the majority of routes via which the probe electroactive species accesses the carbon particles at the electrode surface. The MIP electrode was not sensitive to some molecules structurally similar to VD, suggesting a highly selective nature of the designed sensor. The new VD sensor impedimetric response as a function of the logarithm of VD concentration was found to be linear in the range of 1.0–100.0 pM. The detection limit of the sensor was estimated to be 0.22 pM. The sensor was used for VD level estimation in plasma samples.

Synthesis of highly selective molecularly imprinted nanoparticles by a solid-phase imprinting strategy for fluorescence turn-on recognition of phospholipid

Molecularly imprinted polymers (MIPs) are artificial receptors with template tailored recognition sites complementary to the targets. The versatility of this molecular imprinting technique has been hampered by the lack of practical synthetic procedures to prepare highly selective MIP nanoparticles targeting phospholipids, which are challenging to be imprinted due to their amphiphilic structure. Here, a novel sedimentation-based solid-phase imprinting strategy is introduced relying on polymerization in the presence of template-modified silica nanospheres (SNs). To demonstrate this concept, the sphingosine-1-phosphate receptor agonist fingolimod phosphate (FP) was coupled to SNs which were dispersed in the prepolymerization medium consisting of the fluorescent functional monomer 1,8-bis(N-vinylimidazol-N′-methyl)anthracene bromide and the crosslinking monomer ethyleneglycol dimethacrylate. High dilution polymerization of the dispersion under agitation followed by simple sedimentation-based separation of the SN template resulted in the isolation of surface imprinted fluorescent MIP nanoparticles (FMIP NPs) in a high yield (17 %). The FMIP NPs displayed fluorescence enhancement in response to the template with a high imprinting factor (IF=9) under the experimental conditions and good specificity, and could recognize FP in human serum with recoveries of 68–74 %. Moreover, the template-modified SNs could be recycled for reuse. Such molecular imprinting strategy opens a new approach to produce highly selective artificial receptors targeting phospholipids.

Polytyramine Film-Coated Single-Walled Carbon Nanotube Electrochemical Chemosensor with Molecularly Imprinted Polymer Nanoparticles for Duloxetine-Selective Determination in Human Plasma.

We devised, fabricated, and tested differential pulse voltammetry (DPV) and impedance spectroscopy (EIS) chemosensors for duloxetine (DUL) antidepressant determination in human plasma. Polyacrylic nanoparticles were synthesized by precipitation polymerization and were molecularly imprinted with DUL (DUL-nanoMIPs). Then, together with the single-walled carbon nanotube (SWCNT) scaffolds, they were uniformly embedded in polytyramine films, i.e., nanoMIPs-SWCNT@(polytyramine film) surface constructs, deposited on gold electrodes by potentiodynamic electropolymerization. These constructs constituted recognition units of the chemosensors. The molecular dynamics (MD) designing of DUL-nanoMIPs helped select the most appropriate functional and cross-linking monomers and determine the selectivity of the chemosensor. Three different DUL-nanoMIPs and non-imprinted polymer (nanoNIPs) were prepared with these monomers. DUL-nanoMIPs, synthesized from respective methacrylic acid and ethylene glycol dimethyl acrylate as the functional and cross-linking monomers, revealed the highest affinity to the DUL analyte. The linear dynamic concentration range, extending from 10 pM to 676 nM DUL, and the limit of detection (LOD), equaling 1.6 pM, in the plasma were determined by the DPV chemosensor, outperforming the EIS chemosensor. HPLC-UV measurements confirmed the results of DUL electrochemical chemosensing.

Iodo Silanes as Superior Substrates for the Solid Phase Synthesis of Molecularly Imprinted Polymer Nanoparticles.

Current state-of-the-art techniques for the solid phase synthesis of molecularly imprinted polymer (MIP) nanoparticles typically rely on amino silanes for the immobilisation of template molecules prior to polymerisation. An investigation into commonly used amino silanes identified a number of problematic side reactions which negatively affect the purity and affinity of these polymers. Iodo silanes are presented as a superior alternative in a case study describing the synthesis of MIPs against epitopes of a common cancer biomarker, epidermal growth factor receptor (EGFR). The proposed iodo silane outperformed the amino silane by all metrics tested, showing high purity and specificity, and nanomolar affinity for the target peptide.

Molecularly imprinted polymer enhances affinity and stability over conventional aptasensor for blood clotting biomarker detection on regimented carbon nanohorn and gold nanourchin hybrid layers

This study aims to develop a rapid and sensitive biomimetic biosensor for the early detection of bleeding disorders by sensing human blood clotting factor IX protein (FIX). Authors used a dual sensitive detection strategy to identify FIX deficiency in human plasma, by incorporating aptamer recognition mechanism with molecular imprinted polymer (MIP) technology. Amino-modified truncated 2′ fluoro-RNA aptamer was used as macro-monomer in MIP synthesis. Produced MIP nanoparticles were immobilized through carbodiimide on Archimedean spiral interdigitated electrode surface for the electrical detection. The sensitivity was enhanced by surface modification using carbon nanohorn and gold nanourchin. Incorporating these hybrid materials and MIP, the enhanced FIX sensor sensitivity was at 6.06E-6 µA fM−1 µm−2. It was found that MIP incorporated sensor has 3-folds enhanced sensitivity with 40 fM detection limit compared to the conventional aptasensor. Validations have been given by sensing FIX level from human plasma serum with 10.7 pM sensitivity and by enzyme-linked apta-sorbent assay at 8 pM as a sensitivity. Moreover, the specificity of sensor also has proven with discrimination of the analogues. This research produced a novel biosensor for FIX detection and justifies that aptamer embedded MIP plays a crucial role for high-performance protein recognition in bleeding diathesis.