Gold surface-bound hyperbranched polyethyleneimine (PEI) films decorated with palladium nanoparticles have been used as efficient catalysts for a series of Suzuki reactions. This thin film-format demonstrated good catalytic efficiency (TON up to 3.4 x 10(3)) and stability. Incorporation into a quartz crystal microbalance (QCM) instrument illustrated the potential for using this approach in lab-on-a-chip-based synthesis applications.

Attana’s Quartz Crystal Microbalance (QCM) analytical instruments have been developed to study in vitro biological interactions, mimicking the in vivo conditions. Attana’s superior technology for kinetic interaction studies allows to perform different assays, including biochemical, crude, sera, cell, and tissue-based, in vitro diagnostic and material chemistry assays, in real time and label free. With the focus to validate, select, and optimize drug candidates prior to clinical trials, Attana has helped pharmaceutical companies to increase their efficiency and profitability. In addition, the Attana instruments and services have been used in many other applications and research as described in this chapter.

Background: The interaction between biotin and avidin is utilized in a wide range of assay and diagnostic systems. A robust material capable of binding biotin should offer scope in the development of reusable assay materials and biosensor recognition elements. Results: Biotin-selective thin (3-5 nm) films have been fabricated on hexadecanethiol self assembled monolayer (SAM) coated Au/quartz resonators. The films were prepared based upon a molecular imprinting strategy where N, N'-methylenebisacrylamide and 2-acrylamido-2-methylpropanesulfonic acid were copolymerized and grafted to the SAM-coated surface in the presence of biotin methyl ester using photoinitiation with physisorbed benzophenone. The biotinyl moiety selectivity of the resonators efficiently differentiated biotinylated peptidic or carbohydrate structures from their native counterparts. Conclusions: Molecularly imprinted ultra thin films can be used for the selective recognition of biotinylated structures in a quartz crystal microbalance sensing platform. These films are stable for periods of at least a month. This strategy should prove of interest for use in other sensing and assay systems.

Phage display screening of a surface-immobilized adenine derivative led to the identification of a heptameric peptide with selectivity for adenine as demonstrated through quartz crystal microbalance (QCM) studies. The peptide demonstrated a concentration dependent affinity for an adeninyl moiety decorated surface (KD of 968 ± 53.3 μM), which highlights the power of piezoelectric sensing in the study of weak interactions. 

Metal-catalyzed cross-coupling reactions are among the most important transformations in organic synthesis. However, the use of C−H activation for sp2 C−N bond formation remains one of the major challenges in the field of crosscoupling chemistry. Described herein is the first example of the synergistic combination of copper catalysis and electrocatalysis for aryl C−H amination under mild reaction conditions in an atom-and step-economical manner with the liberation of H2 as the sole and benign byproduct.

Monodisperse magnetic gamma-Fe2O3 nanoparticles (MNPs) were prepared by a simple, improved, one-pot solvothermal synthesis using SDS and PEG 6000 as double capping reagents. This double protecting layer afforded better MNP uniformity (Z average 257 +/- 11.12 nm, PDI = 0.18) and colloidal stability. Materials were characterized by DLS, SEM, TEM, XPS, and XRD. The use of these MNPs in the synthesis of core-shell structures with uniform and tunable silica coatings was demonstrated, as silica coated MNPs are important for use in a range of applications, including magnetic separation and catalysis and as platforms for templated nanogel synthesis.

Oxytocin imprinted polymer nanoparticles were synthesized by glass bead supported solid phase synthesis, with NMR and molecular dynamics studies used to investigate monomer-template interactions. The nanoparticles were characterized by dynamic light scattering, scanning- and transmission electron microscopy and X-ray photoelectron spectroscopy. Investigation of nanoparticle-template recognition using quartz crystal microbalance-based studies revealed sub-nanomolar affinity, k(d) approximate to 0.3 +/- 0.02 nM (standard error of the mean), comparable to that of commercial polyclonal antibodies, k(d) approximate to 0.02-0.2 nM.

A chemosensor for selective recognition of biotinyl moiety has been devised using electropolymerized film and tested against selective biotinylated targets. The sensor comprises biotin molecularly imprinted polymer (MIP) polymeric nanowires, as a recognition element, overlaid on gold-coated quartz transducers. The preparation of nanostructured MIPs and reference systems have been demonstrated using electrochemical copolymerization of the stabilized complex between the template (biotin), the functional monomer (4-aminobenzoic acid), and cross-linker (aniline) and/or sacrificial biotin-modified Al2O3 membrane. Density functional theoretical studies signify formation of a stable hydrogen-bonded complex of biotin with 4-aminobenzoic acid in the pre-polymerization mixture. Scanning electron microscope studies revealed uniformly grown and densely packed polyaniline hierarchical structures. Piezoelectric microgravimetry under flow injection analysis (FIA) conditions revealed selective binding of biotin methyl ester (BtOMe, 4) (79.89 +/- 2.17 Hz/mM) with imprinted polyaniline hierarchical structures over 10 fold higher than the non-imprinted counterpart. The detection limit of the MIP is 50 nM under optimized conditions. Particularly, the sensor selectively recognizes BtOMe from structural or functional analogues, such as thiamine (4.87 +/- 0.10 Hz/mM) and pyridoxamine (12.08 +/- 0.24 Hz/mM). Importantly, the MIP hierarchical structures were shown to be selective for biotinylated targets (biotin moiety labeled cytochrome C, dextran, oxytocin and obestatin). (C) 2018 The Electrochemical Society.

The use of liquid crystalline (LC) media as sacrificial templates during the polymer synthesis has been explored. The LC-media introduce morphological features into resultant polymers which when used together with molecular imprinting can produce materials with hierarchical architectures. Bupivacaine (1) imprinted co-polymers of 2-hydroxyethylmethacrylate (HEMA) (2a) and 1,4-divinylbenzene (DVB) (3a) were synthesized using photochemical initiation in lyotrophic liquid crystalline phases of AOT (5) in water/p-xylene and Triton X-100 (6) /water systems. SEM studies revealed the impact of the LC-media on polymer morphology, with polymer brush-like structures, with bristles of ≈30 nm diameter. The polymer morphology reflects that of the hexagonal phase of the LC medium. The rebinding characteristics of polymer films were evaluated quartz crystal microbalance (QCM, under FIA conditions). The influence of the presence of imprinting-derived recognition sites in AOT (5) in water/p-xylene polymer film induced brush-like features which provided a 25-fold enhancement of sensor sensitivity. This chemosensor was shown to be selective for the local anesthetic template, bupivacaine, through studies using the structural analogues ropivacaine and mepivacaine.

Herein, we report the use of the use of non-ionic deep eutectic solvents (ni-DESs) as porogens in polymer synthesis. Three ni-DES systems, acetamide-N-methylacetamide (AA-NMA), N-methylacetamide-N-methylurea (NMA-NMU) and N-methylacetamide-N,N'-dimethylurea (NMA-NN'DMU), were deployed in the synthesis of a series of cross-linked copolymer monoliths comprised of a functional monomer, methacrylic acid (MAA) or hydroxyethylmethacrylate (HEMA), and a cross-linking monomer, ethylene glycol dimethylacrylate (EGDMA) or divinylbenzene (DVB) or 1,4-bis(acryloyl)piperazine (BAP). Polymers were synthesized under thermally initiated conditions with 2,2'-azobis(2-methylpropionitrile) (AIBN) or 2,2'-azobis(2-amidinopropane) dihydrochloride (ABAH) as an initiator. The resulting polymer monoliths were ground and sieved to yield particles of 63-125 mu m. Corresponding polymers prepared in conventional porogens, acetonitrile, toluene and water were synthesized to serve as controls. The influence of the respective niDESs on polymer morphologies was examined by Brunauer-Emmett-Teller (BET) N2-adsorption, Fourier transform infrared spectroscopy (FT-IR), elemental analysis, scanning electron microscopy (SEM) and zeta potential measurements. The materials displayed surface areas, pore volumes and pore diameters of 115-532 m(2) g(-1), 0.1-1.4 cm(3) g(-1) and 5.2-12.5 nm, generally comparable with those of polymers obtained using conventional solvents, thus presenting these ni-DESs as viable alternatives to conventional organic solvents. The post-polymerization recovery of the ni-DESs (>80%) was demonstrated, highlighting the potential for using these novel liquids as alternatives to conventional, and often more expensive, toxic, flammable or volatile solvents in polymer synthesis.

The development of in silico strategies for the study of the molecular imprinting process and the properties of molecularly imprinted materials has been driven by a growing awareness of the inherent complexity of these systems and even by an increased awareness of the potential of these materials for use in a range of application areas. Here we highlight the development of theoretical and computational strategies that are contributing to an improved understanding of the mechanisms underlying molecularly imprinted material synthesis and performance, and even their rational design.

Recent years have witnessed a dramatic increase in the use of theoretical and computational approaches in the study and development of molecular imprinting systems. These tools are being used to either improve understanding of the mechanisms underlying the function of molecular imprinting systems or for the design of new systems. Here, we present an overview of the literature describing the application of theoretical and computational techniques to the different stages of the molecular imprinting process (pre-polymerization mixture, polymerization process and ligand-molecularly imprinted polymer rebinding), along with an analysis of trends within and the current status of this aspect of the molecular imprinting field.

Theoretical and computational studies of molecular imprinting have helped provide valuable insights concerning the nature of the molecular-level events underlying the recognition characteristics of molecularly imprinted materials. Here, we first present an overview of a thermodynamic treatment of factors governing the behaviour of these functional materials, and then a summary of the development and current status of the use of computational strategies for studying aspects of molecular imprinting and the resulting material properties.

Rapid and accurate serological analysis of SARS-CoV-2 antibodies is important for assessing immune protection from vaccination or infection of individuals and for projecting virus spread within a population. The quartz crystal microbalance (QCM) is a label-free flow-based sensor platform that offers an opportunity to detect the binding of a fluid-phase ligand to an immobilized target molecule in real time. A QCM-based assay was developed for the detection of SARS-CoV-2 antibody binding and evaluated for assay reproducibility. The assay was cross-compared to the Roche electrochemiluminescence assay (ECLIA) Elecsys (R) Anti-SARS-CoV-2 serology test kit and YHLO's chemiluminescence immunoassay (CLIA). The day-to-day reproducibility of the assay had a correlation of r(2) = 0.99, p < 0.001. The assay linearity was r(2) = 0.96, p < 0.001, for dilution in both serum and buffer. In the cross-comparison analysis of 119 human serum samples, 59 were positive in the Roche, 52 in the YHLO, and 48 in the QCM immunoassay. Despite differences in the detection method and antigen used for antibody capture, there was good coherence between the assays, 80-100% for positive and 96-100% for negative test results. In summation, the QCM-based SARS-CoV-2 IgG immunoassay showed high reproducibility and linearity, along with good coherence with the ELISA-based assays. Still, factors including antibody titer and antigen-binding affinity may differentially affect the various assays' responses.

Significant enantioselective recognition has been achieved through the introduction of long range ordered and highly interconnected 300 nm diameter pores in molecularly imprinted polymer matrices.

The growing demand for lithium-ion batteries (LiBs) for the electronic and automobile industries combined with the limited availability of key metal components, in particular cobalt, drives the need for efficient methods for the recovery and recycling of these materials from battery waste. Herein, we introduce a novel and efficient approach for the extraction of cobalt, and other metal components, from spent LiBs using a nonionic deep eutectic solvent (ni-DES) comprised of N-methylurea and acetamide under relatively mild conditions. Cobalt could be recovered from lithium cobalt oxide-based LiBs with an extraction efficiency of >97% and used to fabricate new batteries. The N-methylurea was found to act as both a solvent component and a reagent, the mechanism of which was elucidated.

Hierarchically nanostructured chloramphenicol (CLP) imprinted thin polymer films have been developed using a renewable monomer, the antioxidant caffeic acid (CA), using sacrificial nanostructures to induce porosity into the films. The poly(caffeic acid) (PCA) films were synthesized on Au/quartz resonators via greener polymerization conditions (clean energy electropolymerization in aqueous buffer or a non-ionic deep eutectic solvent). The sacrificial nanostructures explored included zein-based protein nanobeads, anodized alumina membrane, and Tween 20-derived polysorbate micelles, where dissolution of the sacrificial nanostructure templates from the PCA films afforded uniform long-range hyperporous networks, nanowires and nanoparticles, respectively, as revealed by SEM studies. Selective extraction of the CLP template from PCA films, was monitored by XPS, and afforded CLP selective cavities. The CLP-imprinted PCA(zein) films demonstrated eight- to 25-fold higher sensitivity than the other nanostructures in a QCM-sensor format, the limit of detection (LOD) under optimized FIA conditions was 50 mM. Significant sensitivities for CLP in milk were observed (1.5 mu g/ml to 3 mg/ml), covering the clinically relevant concentration range. The PCA(zein) thin films selectively differentiate CLP from structurally related antibiotics and are robust. Their production from renewable feedstocks of biological origin highlights the potential of this class of nanostructured materials for applications utilizing thin films.

A novel hyperbranched polyethyleneimine (PEI) modified gold surface has been designed, fabricated, and investigated with respect to its ability to resist non-specific adsorption of proteins. The facile synthesis strategy, based on self-assembly, involves immobilization of polyethyleneimine to gold surfaces modified with 11-mercaptoundecanoic acid (MuDA) monolayers using traditional carbodiimide chemistry. The hyperbranched polymer brushes were characterized by X-ray photoelectron spectroscopy (XPS). Reflection absorption infrared spectroscopy (RAIRS) and ellipsometry measurements showed the thickness of the PEI brushes increases with adsorption solution ionic strength. Polymer brush surface concentrations can be improved from 2560 to 3880 chains/mu m(2) by changing the ionic strength of the adsorption solution (PBS) by varying NaCl concentration from 0 to 650 mM. Protein adsorption (pH 7.4) was evaluated under flow injection analysis (FIA) conditions using a quartz crystal microbalance (QCM). The PEI brushes suppress protein adsorption, for example, cytochrome C, bovine serum albumin (BSA), and ribonuclease A, to less than 0.08 mu g/cm(2) and the protein resistance increases with increasing ionic strength of the carrier solution, performance comparable to that achieved with comparable PEG-coated surfaces. The PEI brushes were exceptionally stable, with adsorption characteristics maintained after 6 months storage in aqueous conditions (pH 7.4, 25 degrees C, PBS). The potential of hyperbranched PEI structures as protein-resistant surfaces is discussed. (C) 2013 Elsevier Inc. All rights reserved.

A chemosensor utilizing electro-polymerized film, as recognition element, has been devised and tested for selective determination of aspirin. The sensor consists of molecularly imprinted polymer (MIP) recognition elements electrodeposited as polymeric nanowires on gold-coated quartz resonator. A nano structures were prepared by electrochemical co-polymerization of the preformed complex between the template, aspirin, the functional monomers, 3-thienylboronic acid (3-TBA) and 3-thiopheneacetic acid (3-TAA), and thiophene, which was employed as a cross-linker. This nanostructure upon leaching aspirin serve as MIP. Polymerizations were performed in acetonitrile (MIP-org) as well as a micelle forming medium (MIP-mic). For MIP nanowire (MIP-ano) synthesis, sacrificial alumina templates were used during electro-polymerization in acetonitrile. Scanning electron microscope studies revealed compactly arranged polythiophene nanowires of uniform thickness in MIP-ano film, and MIP-mic film produced aggregated micron sized polymer structures. Density functional theoretical studies indicated a stable hydrogen bond-based complexation of aspirin by 3-TBA and 3-TAA in the pre-polymerization mixture implying that the MIP film thus prepared could selectively rebind the aspirin template. The MIP-ano-based chemosensor was sensitive towards aspirin (0.5-10 mM), over clinically relevant range (0.15-0.5 mM) under optimized FIA conditions. The sensitivity (20.62 Hz/mM) of the MIP-ano was eight and fifteen times higher than the MIP-mic (2.80 Hz/mM) and MIP-org (1.10 Hz/mM). Notably, the sensor selectively discriminates aspirin from structurally or functionally related interferants and metabolites, such as, salicylic acid, acetylsalicyloyl chloride and ibuprofen. (C) 2017 Elsevier B.V. All rights reserved.

Proteinaceous, tunable nanostructures of zein (prolamine of corn) were developed as biotinyl-specific receptors using a molecular imprinting technique. Sacrificial templates, such as latex beads (LB3) and anodized alumina membrane (AAM), have been used to control nanostructural patterns in biotin-imprinted zein (BMZ). Briefly, a methanolic solution of the zein-biotin complex was drop cast upon a self-organized LB3 and AAM templates on Au/quartz surfaces. Subsequent dissolution of these sacrificial templates affords highly oriented, predetermined, and uniformly grown hyperporous (300 nm) and nanowires (150 nm) motifs of zein (BMZ-LB3 and BMZ-AAM), as shown by scanning electron microscopy (SEM). Selective extraction of biotin molecular template cast-off site -selective biotin imprints within these zein nanostructures complementary to biotinyl moieties. Alternatively, biotin-imprinted zein nanoparticles (BMZ-Np) and thin film (BMZ-MeOH) were prepared by coacervation and drop casting methods, respectively. Density functional theoretical (DFT) studies reveal strong hydrogen-bonded interaction of biotin with serine and glutamine residues of zein. Quartz crystal microbalance (QCM) studies show remarkable sensitivity of the hyperporous-BMZ-LB3 and nanowires of BMZ-AAM towards biotin derivative (biotin methyl ester) by five (24.75 +/- 1.34 Hz/mM) and four (18.19 +/- 0.75 Hz/mM) times, respectively, higher than the BMZ-MeOH. Enhanced permeability features of the zein nanostructures, when templated with LB3, enable the QCM detection of biotin-or its derivatives down to 12.9 ng mL-1 from dairy products (Kefir). The outcome of this study shall be a key aspect in interfacing biological materials with micro-/nano-sensors and electronic devices for detecting pertinent analytes using sustainably developed biopolymer-based nanostructures.

Nanostructured bupivacaine-selective molecularly imprinted 3-aminophenylboronic acid-p-phenylenediamine co-polymer (MIP) films have been prepared on gold-coated quartz (Au/quartz) resonators by electrochemical synthesis under cyclic voltammetric conditions in a liquid crystalline (LC) medium (triton X-100/water). Films prepared in water and in the absence of template were used for control studies. Infrared spectroscopic studies demonstrated comparable chemical compositions for LC and control polymer films. SEM studies revealed that the topologies of the molecularly imprinted polymer films prepared in the LC medium (LC-MIP) exhibit discernible 40 nm thick nano-fiber structures, quite unlike the polymers prepared in the absence of the LC-phase. The sensitivity of the LC-MIP in a quartz crystal microbalance (QCM) sensor platform was 67.6 ± 4.9 Hz/mM under flow injection analysis (FIA) conditions, which was ≈250% higher than for the sensor prepared using the aqueous medium. Detection was possible at 100 nM (30 ng/mL), and discrimination of bupivacaine from closely related structural analogs was readily achieved as reflected in the corresponding stability constants of the MIP-analyte complexes. The facile fabrication and significant enhancement in sensor sensitivity together highlight the potential of this LC-based imprinting strategy for fabrication of polymeric materials with hierarchical architectures, in particular for use in surface-dependent application areas, e.g., biomaterials or sensing.

Nano-structured materials are used in electronics, diagnostics, therapeutics, smart packaging, energy management and textiles, areas critical for society and quality of life. However, their fabrication often places high demands on limited natural resources. Accordingly, renewable sources for the feedstocks used in their production are highly desirable. We demonstrate the use of readily available biopolymers derived from maize (zein), milk (casein) and malacostraca (crab-shell derived chitin) in conjunction with sacrificial templates, self-assembled monodisperse latex beads and anodized aluminium membranes, for producing robust surfaces coated with highly regular hyperporous networks or wire-like morphological features, respectively. The utility of this facile strategy for nano-structuring of biopolymers was demonstrated in a surface based-sensing application, where biotin-selective binding sites were generated in the zein-based nano-structured hyperporous network.

A family of non-ionic deep eutectic liquids has been developed based upon mixtures of solid N-alkyl derivatives of urea and acetamide that in some cases have melting points below room temperature. The eutectic behaviour and physical characteristics of a series of eleven eutectic mixtures are presented, along with a molecular dynamics study-supported hypothesis for the origin of the non-ideal mixing of these substances. Their use as solvents in applications ranging from natural product extraction to organic and polymer synthesis are demonstrated.

Controlled on-surface synthesis of polymer films using amide-based, environmentally friendly, nonionic deep eutectic solvents (ni-DESs) has been developed to regulate the porous features of the films. An appropriate combination of acetamide (A), urea (U), and their methyl derivatives (N-methylacetamide (NMA) and N-methylurea (NMU)) was used to prepare ni-DES. Polymer films were electrosynthesized using 4-aminobenzoic acid (4-ABA) and pyrrole as monomers in ni-DESs. We presumed that the flickering-cluster-like complexes and the extended H-bond networks in ni-DESs enhance the porosity of the polymer films, thus improving permeability features, as reflected in sensor performance. Electrosynthesized polymer films, imprinted with biotin templates (MIPs), have been tested as receptors for biotinylated targets. Molecular dynamics simulations of the prepolymerization mixture revealed the formed complexes between 4-ABA and biotin comprising high-frequency H-bonds. X-ray photoelectron spectroscopy (XPS) and reflection absorption infrared spectroscopy (RAIRS) studies revealed the structural integrity in the polymer films irrespective of the medium. Scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS) measurements showed a highly corrugated and porous nature for MIPA-U and MIPNMU-U when prepared in A-U and NMU-U ni-DESs. Atomic force microscope (AFM) studies support these observations, displaying an enhancement in the surface roughness from 1.44 nm (MIPaqueous) to 23.6 nm (MIPNMU-U). QCM analysis demonstrated a remarkable improvement in sensitivity of MIPA-U (17.99 +/- 0.72 Hz/mM) and MIPNMU-U (18.40 +/- 0.81 Hz/mM) films toward the biotin methyl ester (BtOMe, biotin derivative) than the MIPaqueous film. The chemosensor devised with the above MIP recognition films selectively recognized BtOMe (LOD = 12.5 ng/mL) and biotinylated biomolecules, as shown by the stability constant K-s values (MIPA-U = 1442 and MIPNMU-U = 1502 M-1). The porous network generated in the polymer films by the flickering-cluster-like complexes present in the ni-DES facilitates the analyte diffusion and recognition. We propose this ni-DES as an economically advantageous and environmentally friendly alternative to conventional ionic liquids and organic solvents in polymer synthesis and to influence polymer morphology for developing hierarchical materials.

Macroporous polymer films with long-range uniformity and biotinyl-moiety selective recognition sites have been developed. A hierarchical molecular imprinting strategy afforded significant enhancements in quartz crystal microbalance (QCM) sensitivities towards biotinylated compounds.