Electrochemical Detection of Gallic Acid-Capped Gold Nanoparticles Using a Multiwalled Carbon Nanotube-Reduced Graphene Oxide Nanocomposite Electrode.

Recently, a plethora of ecofriendly methods have been developed for the synthesis of AuNPs using a multitude of biogenic agents. Polyphenols from plants are particularly attractive for producing AuNPs because in addition to helping with the synthesis of AuNPs, the polyphenol capping of the NPs can be used as a platform for versatile applications. Polyphenol-capped AuNPs could also make the detection of AuNPs possible, should they be released into the environment. Because polyphenols are redox-active, they can be used as a probe to detect AuNPs using electrochemical techniques. In this work, we have developed an MWCNT-rGO nanocomposite electrode for the sensitive detection of AuNPs capped with gallic acid (GA, a green-tea-derived polyphenol) using differential pulse voltammetry (DPV). The reduction of gallic acid-capped AuNPs was used as the quantification signal, and the calibration curve displayed a detection limit of 2.57 pM. Using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS), we have shown that the modification of the electrode surface with an MWCNT-rGO hybrid nanocomposite resulted in a 10-fold increase in current response leading to the sensitive detection of GA-AuNPs compared to unmodified electrodes. We have also demonstrated the applicability of the electrochemical sensor in detecting GA-AuNPs in various analytical matrixes such as human serum and natural creek water (Highland Creek, ON) with good recovery.

TiO2-coated 2D photonic crystals for reflectometric determination of malachite green.

A "detect and destroy" strategy is reported for the spectroscopic determination and photocatalytic degradation of Malachite Green (MG) in aqueous solutions. The intensity of the reflection peak maxima from the TiO2-coated 2D-photonic crystal (PhC) at 633 nm wavelength undergoes a gradual decrease with increasing concentrations of MG. The determination of MG was readily achieved in the nanomolar range due to the quenching of the reflection intensity of the peak, measured using a fiber optic probe. The assay works in the 1.0 nM to 10 µM MG concentration range with a detection limit of 1.3 nM. The same TiO2-coated 2D-PhC surface can photocatalytically degrade MG in aqueous solutions under UV irradiation. The photocatalytic degradation in the presence of TiO2-coated 2D-PhC becomes evident as the blue color of MG changes to colorless with increasing irradiation time. The decrease in absorption is detected at 617 nm. It was found that the photocatalytic efficiency of TiO2 was synergistically enhanced in the presence of 2D-PhCs. It is concluded that each component of the TiO2-coated 2D-PhC system plays a key role in the detection and degradation of MG. Graphical abstractSchematic representation for reflectometric detection and photocatalytic degradation of hazardous Malachite Green dye using TiO2-coated two-dimensional photonic crystals.

Epigallocatechin Gallate-Modified Graphite Paste Electrode for Simultaneous Detection of Redox-Active Biomolecules.

In this study, simultaneous electrochemical detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) was performed using a modified graphite paste electrode (MGPE) with epigallocatechin gallate (EGCG) and green tea (GT) powder. It was shown that the anodic peak current increased in comparison with that of the graphite paste electrode (GPE) in the cyclic voltammograms. The optimal pH for simultaneous determination of a quaternary mixture of AA-DA-UA was determined to be pH 2. The anodic peak potentials for a mixture containing AA-DA-UA were well separated from each other. The catalytic peak currents obtained at the surface of the MGPE/EGCG were linearly dependent on the AA, DA, and UA concentrations up to 23, 14, and 14 µM, respectively. The detection limits for AA, DA, and UA were 190, 90, and 70 nM, respectively. The analytical performance of this sensor has been evaluated for simultaneous detection of AA, DA, and UA in real samples. Finally, a modified electrode was prepared using GT and used for simultaneous determination of AA, DA, and UA. Based on the results, MPGE/GT showed two oxidation peaks at 0.43 and 0.6 V for DA and UA, respectively, without any oxidation peak for AA. The calibration curves at the surface of MGPE/GT were linear up to 14 µM with a detection limit of 0.18 and 0.33 µM for DA and UA, respectively. MGPEs provide a promising platform for the future development of sensors for multiplexed electrochemical detection of clinically important analytes.

Electrochemical immunosensors for effective evaluation of amyloid-beta modulators on oligomeric and fibrillar aggregation processes.

A novel electrochemical immunosensor fabricated from gold compact disc electrodes was designed for rapid evaluation of aggregation processes that lead to the formation of oligomeric and fibrillar states of amyloid-beta(1-42) (Aß(1-42)) during Alzheimer's disease. Conformation-specific antibodies were immobilized on the surface of the gold electrode using a 3,3'-dithiobis (sulfosuccinimidyl) propionate (DTSSP) linker. Surface binding events were analyzed by electrochemical impedance spectroscopy (EIS) in which the formation of an antigen-antibody complex was quantified as a function of charge transfer resistance using a [Fe(CN)6](3-/4-) redox probe. The effectiveness of novel sym-triazine-derived aggregation modulators (TAE-1, TAE-2) to reduce the population of toxic oligomers was evaluated. Aß fibril formation was validated by thioflavin T (ThT) fluorescence, whereas oligomer formation was investigated by MALDI. Antigen detection by EIS was further supported by immuno dot blot assays for oligomeric and fibrillar components. Docking simulations of the aggregation modulators TAE-1 and TAE-2 with Aß(1-42) fibrils performed using Autodock Vina suggest a mechanism for the improved aggregation inhibition observed for TAE-2. The results demonstrate the utility and convenience of impedance immunosensing as an analytical tool for rapid and comprehensive evaluation of effective Aß aggregation modulating agents.

Quantum dot based fluorometric detection of cancer TF-antigen.

Cancer is a major global health challenge that would benefit from advances in screening methods for early detection that are rapid and low cost. TF-antigen is a tumor-associated antigen displayed on cell surface proteins of a high percentage of human carcinomas. Here we present a fluorometric bioassay for TF-antigen (galactose-ß-(1→3)-N-acetyl-d-galactosamine) that utilizes quantum dot (QD) technology coupled with magnetic beads for rapid detection of TF-antigen at high sensitivity (10(-7) M range). In the competitive bioassay, 4-aminophenyl ß-d-galactopyranoside (4-APG) conjugated to QDs competes with TF-antigen for binding sites on peanut agglutinin (PNA) that is immobilized on magnetic beads. The bioassay is specific and ultrasensitive in the environment of complex protein mixtures, demonstrating its potential applicability for the screening of clinical samples.

Diazonium-Modified Screen-Printed Electrodes for Immunosensing Growth Hormone in Blood Samples.

Altered growth hormone (GH) levels represent a major global health challenge that would benefit from advances in screening methods that are rapid and low cost. Here, we present a miniaturized immunosensor using disposable screen-printed carbon electrodes (SPCEs) for the detection of GH with high sensitivity. The diazonium-based linker layer was electrochemically deposited onto SPCE surfaces, and subsequently activated using covalent agents to immobilize monoclonal anti-GH antibodies as the sensing layer. The surface modifications were monitored using contact angle measurements and X-ray photoelectron spectroscopy (XPS). The dissociation constant, Kd, of the anti-GH antibodies was also determined as 1.44 (±0.15) using surface plasmon resonance (SPR). The immunosensor was able to detect GH in the picomolar range using a 20 µL sample volume in connection with electrochemical impedance spectroscopy (EIS). The selectivity of the SPCE-based immunosensors was also challenged with whole blood and serum samples collected at various development stages of rats, demonstrating the potential applicability for detection in biological samples. Our results demonstrated that SPCEs provided the development of low-cost and single-use electrochemical immunosensors in comparison with glassy carbon electrode (GCE)-based ones.

Carbon ceramic microelectrodes modified with buckyballs for simultaneous determination of redox-active biomolecules.

In this report, simultaneous electrochemical determination of ascorbic acid (AA), dopamine (DA), uric acid (UA) and tryptophan (Trp) was achieved using buckyball-modified carbon ceramic microelectrodes (CCMEs). A concentration-dependent increase in anodic peak current signals was observed in comparison with those obtained at bare CCMEs. The optimal pH for simultaneous determination of a quaternary mixture of AA-DA-UA-Trp was determined to be pH 4. The peak separations for the mixture containing AA-DA-UA-Trp were well-defined at the scan rate of 50 mV s-1. The catalytic peak current obtained was linearly dependent on the AA, DA, UA and Trp concentrations in the range of 6.0-600, 6.0-600, 6.0-600 and 4.0-440 µM, respectively. The detection limits for AA, DA, UA and Trp were also determined to be 1.64, 0.82, 0.36 and 1.22 µM, respectively. The analytical performance of this sensor has also been challenged for simultaneous electrochemical detection of AA, DA, UA and Trp in real samples.

Biological activity of sym-triazines with acetylcholine-like substitutions as multitarget modulators of Alzheimer's disease.

The bioactivities of two novel compounds (TAE-1 and TAE-2) that contain a sym-triazine scaffold with acetylcholine-like substitutions are examined as promising candidate agents against Alzheimer's disease. Inhibition of amyloid-ß fibril formation in the presence of Aß1-42, evaluated by Thioflavin T fluorescence, demonstrated comparable or improved activity to a previously reported pentapeptide-based fibrillogenesis inhibitor, iAß5p. Destabilization of Aß1-42 assemblies by TAE-1 and TAE-2 was confirmed by scanning electron microscopy imaging. sym-Triazine inhibition of acetylcholinesterase (AChE) activity was observed in cytosol extracted from differentiated human SH-SY5Y neuronal cells and also using human erythrocyte AChE. The sym-triazine derivatives were well tolerated by these cells and promoted beneficial effects on human neurons, upregulating expression of synaptophysin, a synaptic marker protein, and MAP2, a neuronal differentiation marker.

sym-Triazines for directed multitarget modulation of cholinesterases and amyloid-ß in Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurodegenerative disorder marked by numerous causative factors of disease progression, termed pathologies. We report here the synthesis of a small library of novel sym-triazine compounds designed for targeted modulation of multiple pathologies related to AD, specifically human acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and Aß aggregation. Rational targeting of AChE was achieved by the incorporation of acetylcholine substrate analogues into a sym-triazine core in either a mono-, di-, or trisubstituted regime. A subset of these derivatives demonstrated improved activity compared to several commercially available cholinesterase inhibitors. High AChE/BuChE selectivity was characteristic of all derivatives, and AChE steady-state kinetics indicated a mixed-type inhibition mechanism. Further integration of multiple hydrophobic phenyl units allowed for improved ß-sheet intercalation into amyloid aggregates. Several highly effective structures exhibited fibril inhibition greater than the previously reported ß-sheet-disrupting penta-peptide, iAß5p, evaluated by thioflavin T fluorescence spectroscopy and transmission electron microscopy. Highly effective sym-triazines were shown to be well tolerated by differentiated human neuronal cells, as demonstrated by the absence of adverse effects on cellular viability at a wide range of concentrations. Parallel targeting of multiple pathologies using sym-triazines is presented here as an effective strategy to address the complex, multifactorial nature of AD progression.