Latest Trends in Electrochemical Sensors for Neurotransmitters: A Review
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paper_title: Conducting polymer-based electrochemical biosensors for neurotransmitters: A review

paper_content:

Abstract Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.
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paper_title: Separation of fine particles using rotating tube with alternate flow

paper_content:

A new method for selective separation of fine particles was developed by using a rotating tube with alternate flow (RAF). The separation is performed in the condition of negligible small of the centrifugal force of a particle compared to gravity. In the horizontal tube with stable flow, each particle moves along the flow drawing a helical path. The locus of each particle depends on a parameter Aω/V0, where A is a radius of the tube, ω is its angular velocity, and V0 is the sedimentation velocity in a liquid at fixed temperature. The velocity along the flow is determined by the locus and the distribution of the flow speed in the tube. The ratio V/Umax (where V is the particle velocity and Umax is the flow speed at the tube center) was obtained theoretically and experimentally. The value took the maximum at Aω/V0≂2 and decreased near exponentially within the range of Aω/V0≳2.5 and precipitously decreased within Aω/V0≲2. By using an alternate flow method with suitable rotation for each directional flow, larg...
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paper_title: DNA-Based Sensor for the Detection of an Organophosphorus Pesticide: Profenofos

paper_content:

In this work, we propose an electrochemical DNA aptasensor for the detection of profenofos, an organophosphorus pesticide, based on a competitive format and disposable graphite screen-printed electrodes (GSPEs). A thiol-tethered DNA capture probe, which results to be complementary to the chosen aptamer sequence, was immobilised on gold nanoparticles/polyaniline composite film-modified electrodes (AuNPs/PANI/GSPE). Different profenofos solutions containing a fixed amount of the biotinylated DNA aptamer were dropped onto the realized aptasensors. The hybridisation reaction was measured using a streptavidin-alkaline phosphatase enzyme conjugate, which catalyses the hydrolysis of 1-naphthyl -phosphate. The 1-naphtol enzymatic product was detected by means of differential pulse voltammetry (DPV). The aptasensor showed itself to work as a signal off sensor, according to the competitive format used. A dose response curve was obtained between 0.10 μM and 10 μM with a detection limit of 0.27 μM.
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paper_title: Clinical implications and electrochemical biosensing of monoamine neurotransmitters in body fluids, in vitro, in vivo, and ex vivo models

paper_content:

Monoamine neurotransmitters (MNTs) belong to one of the most important groups of neurotransmitters in the central nervous system. They play crucial role in functioning of cardiovascular, renal, and hormonal systems along with establishing human brain-body integration. Abnormal level of MNT is associated with numerous psychotic (schizophrenia, depression, dementia, etc.) and neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's disease, etc.), therefore their sensitive and robust detection is of great clinical significance. Electrochemical detection (ECD) techniques have been paving the path in this direction, for more than four decades now. Keeping the immense importance of MNTs in mind, this review has been formulated to describe fundamentals of MNTs followed by their clinical significance in neuroscience. Herein, we have emphasized on the ECD of MNTs, in various matrices reported till date. In order to provide information on ECD of MNTs in clinically comparable systems, we have included a comprehensive discussion on sensor design and its analytical performance towards analyzing MNTs in the in vitro, in vivo, and ex vivo models. An extensive table is also incorporated to provide better understanding of the role of MNTs in various clinical conditions. Furthermore, this review briefly discusses the challenges faced with EC sensing techniques and loopholes present in current research works. Apart from this, three extended tables are also included in this review, to provide an insight into the amount of work done in ECD of MNTs in last ten years (2008-2018). These tables comprehensively discuss sensor fabrication strategies for determining MNTs in various matrices and models along with their mode of detection and analytical performance.
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paper_title: Conducting polymer nanostructures and their application in biosensors.

paper_content:

Nowadays, functionalized conducting polymer nanomaterials have been received great attention in nanoscience and nanotechnology because of their large surface area. This article reviews various methods for synthesis of conducting polymer nanostructures and their applications in sensing materials, focusing on hard-template, soft-template and other methods and the formation mechanism of conducting polymer nanostructures by these methods. Conducting polymer nanostructures, such as nanotubes, nanowires, and nanoparticles, as sensing platforms for various applications are also summarized.
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paper_title: Conducting polymer-based electrochemical biosensors for neurotransmitters: A review

paper_content:

Abstract Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.
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paper_title: An electrochemical sensor for detection of neurotransmitter-acetylcholine using metal nanoparticles, 2D material and conducting polymer modified electrode.

paper_content:

An essential biological sensor for acetylcholine (ACh) detection is constructed by immobilizing enzymes, acetylcholinesterase (AChE) and choline oxidase (ChO), on the surface of iron oxide nanoparticles (Fe2O3NPs), poly(3,4-ethylenedioxythiophene) (PEDOT)-reduced graphene oxide (rGO) nanocomposite modified fluorine doped tin oxide (FTO). The qualitative and quantitative measurements of nanocomposites properties were accomplished by scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). This prepared biological sensor delineated a wide linear range of 4.0nM to 800μM with a response time less than 4s and detection limit (based on S/N ratio) of 4.0nM. The sensor showed perfect sensitivity, excessive selectivity and stability for longer period of time during storage. Besides its very high-sensitivity, the biosensor has displayed a low detection limit which is reported for the first time in comparison to previously reported ACh sensors. By fabricating Fe2O3NPs/rGO/PEDOT modified FTO electrode for determining ACh level in serum samples, the applicability of biosensor has increased immensely as the detection of the level neurotransmitter is first priority for patients suffering from memory loss or Alzheimer's disease (AD).
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paper_title: Applications of conducting polymer composites to electrochemical sensors: A review

paper_content:

Abstract Conducting polymers (CPs) constitute an important class of organic functional materials. Their unique physical and electrical properties and being inexpensive, easy to synthesize, and suitable matrices for biomolecule immobilization have enabled them to find a wide range of use, including playing roles in supercapacitors, batteries, electrochromic devices, solar cells, sensors, and biomedical applications. To enhance the performance of the CPs, various composite materials have been synthesized with carbon-based materials, metals or metal oxides, etc. This review comprehensively discusses CPs and their composites, followed by their applications. The purpose of this review is to summarize the electrochemical sensors that are based on CPs and their composites and to address future aspects of electrochemical sensing materials.
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paper_title: Electrochemical Analysis of Neurotransmitters.

paper_content:

Chemical signaling through the release of neurotransmitters into the extracellular space is the primary means of communication between neurons. More than four decades ago, Ralph Adams and his colleagues realized the utility of electrochemical methods for the study of easily oxidizable neurotransmitters, such as dopamine, norepinephrine, and serotonin and their metabolites. Today, electrochemical techniques are frequently coupled to microelectrodes to enable spatially resolved recordings of rapid neurotransmitter dynamics in a variety of biological preparations spanning from single cells to the intact brain of behaving animals. In this review, we provide a basic overview of the principles underlying constant-potential amperometry and fast-scan cyclic voltammetry, the most commonly employed electrochemical techniques, and the general application of these methods to the study of neurotransmission. We thereafter discuss several recent developments in sensor design and experimental methodology that are challenging the current limitations defining the application of electrochemical methods to neurotransmitter measurements.
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paper_title: DNA-Based Sensor for the Detection of an Organophosphorus Pesticide: Profenofos

paper_content:

In this work, we propose an electrochemical DNA aptasensor for the detection of profenofos, an organophosphorus pesticide, based on a competitive format and disposable graphite screen-printed electrodes (GSPEs). A thiol-tethered DNA capture probe, which results to be complementary to the chosen aptamer sequence, was immobilised on gold nanoparticles/polyaniline composite film-modified electrodes (AuNPs/PANI/GSPE). Different profenofos solutions containing a fixed amount of the biotinylated DNA aptamer were dropped onto the realized aptasensors. The hybridisation reaction was measured using a streptavidin-alkaline phosphatase enzyme conjugate, which catalyses the hydrolysis of 1-naphthyl -phosphate. The 1-naphtol enzymatic product was detected by means of differential pulse voltammetry (DPV). The aptasensor showed itself to work as a signal off sensor, according to the competitive format used. A dose response curve was obtained between 0.10 μM and 10 μM with a detection limit of 0.27 μM.
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paper_title: Detection of Glutamate and Acetylcholine with Organic Electrochemical Transistors Based on Conducting Polymer/Platinum Nanoparticle Composites

paper_content:

The aim of the study is to open a new scope for organic electrochemical transistors based on PEDOT:PSS, a material blend known for its stability and reliability. These devices can leverage molecular electrocatalysis by incorporating small amounts of nano-catalyst during the transistor manufacturing (spin coating). This methodology is very simple to implement using the know-how of nanochemistry and results in efficient enzymatic activity transduction, in this case utilizing choline oxidase and glutamate oxidase.
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paper_title: CTAB functionalized graphene oxide/multiwalled carbon nanotube composite modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid and nitrite

paper_content:

Abstract We have developed hexadecyl trimethyl ammonium bromide (CTAB) functionalized graphene oxide (GO)/multiwalled carbon nanotubes (MWNTs) modified glassy carbon electrode (CTAB-GO/MWNT) as a novel system for the simultaneous determination of dopamine (DA), ascorbic acid (AA), uric acid (UA) and nitrite (NO 2 − ). The combination of graphene oxide and MWNTs endow the biosensor with large surface area, good biological compatibility, electricity and stability, high selectivity and sensitivity. In the fourfold co-existence system, the linear calibration plots for AA, DA, UA and NO 2 − were obtained over the range of 5.0–300 μM, 5.0–500 μM, 3.0–60 μM and 5.0–800 μM with detection limits of 1.0 μM, 1.5 μM, 1.0 μM and 1.5 μM, respectively. In addition, the modified biosensor was applied to the determination of AA, DA, UA and NO 2 − in urine samples by using standard adding method with satisfactory results.
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paper_title: Direct Electrochemical Detection of Glutamate, Acetylcholine, Choline, and Adenosine Using Non-Enzymatic Electrodes

paper_content:

Non-electroactive neurotransmitters such as glutamate, acetylcholine, choline, and adenosine play a critical role in proper activity of living organisms, particularly in the nervous system. While enzyme-based sensing of this type of neurotransmitter has been a research interest for years, non-enzymatic approaches are gaining more attention because of their stability and low cost. Accordingly, this focused review aims to give a summary of the state of the art of non-enzymatic electrochemical sensors used for detection of neurotransmitter that lack an electrochemically active component. In place of using enzymes, transition metal materials such as those based on nickel show an acceptable level of catalytic activity for neurotransmitter sensing. They benefit from fast electron transport properties and high surface energy and their catalytic activity can be much improved if their surface is modified with nanomaterials such as carbon nanotubes and platinum nanoparticles. However, a general comparison reveals that the performance of non-enzymatic biosensors is still lower than those that use enzyme-based methods. Nevertheless, their excellent stability demonstrates that non-enzymatic neurotransmitter sensors warrant additional research in order to advance them toward becoming an acceptable replacement for the more expensive enzyme-based sensors.
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paper_title: Multi mimetic Graphene Palladium nanocomposite based colorimetric paper sensor for the detection of neurotransmitters

paper_content:

Abstract Palladium in the form of G-Pd nanocomposite possesses multiple enzyme mimicking activity. It catalyzes the oxidation of dopamine, glutamate, H2O2 and NADH through dopamine oxidase, glutamate oxidase, peroxidase and NADH oxidoreductase biomimetic activity. Kinetic studies were performed to calculate the catalytic parameters of G-Pd nanocomposite towards the substrates for a potential heterogeneous catalyst. Among them, glutamate oxidase activity was coupled with peroxidase activity of G-Pd for the detection of glutamate, in the form of a paper based sensor. Analytical performance of G-Pd nanocomposite catalyzed glutamate detection was characterized, and found to be linear in the range 0–400 μM and 400–8000 μM with limit of detection and quantification of 49.4 μM and 117.9 μM respectively. Results from the present study provides substantial progress in the practical application of nanomaterials as heterogeneous catalysts with multi enzyme mimicking property. G-Pd nanocomposite overcomes the complexity of enzyme based biosensors due to less number of reagents, better stability due to the absence of enzymes with mild storage conditions. Multi-mimetic catalytic activity of Pd will find applications in the field of analytical chemistry, biosensors, energy, environment and food safety.
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paper_title: Electrochemical sensors based on carbon nanomaterials for acetaminophen detection: A review.

paper_content:

This study describes the advancements made over the last five years in the development of electrochemical sensors and biosensors for acetaminophen detection. This study reviews the different configurations based on unmodified and chemically modified carbon nanotubes and graphene. The influence of various modifiers on the two types of materials is presented along with their role on the enhancement of the selectivity and sensitivity of (bio)sensors. The review is focused on a comparative description of the applications of carbon-based nanomaterials towards acetaminophen detection and presents the results in a critical manner.
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paper_title: Poly-xanthurenic acid modified electrodes: An amperometric sensor for the simultaneous determination of ascorbic and uric acids

paper_content:

Abstract The poly-xanthurenic acid (poly-Xa)/multi-walled carbon nanotube (MWCNT)/glassy carbon modified electrode (poly-Xa/MWCNT/GCE) was successfully applied for the simultaneous determination of ascorbic (AA) and uric (UA) acids. Cyclic voltammetric results show that the modified electrode displays an excellent eletrocatalytic activity toward the oxidation of AA at a low potential (0.05 V versus Ag/AgCl) and anodic peak resolution (Δ E pa ), close to 300 mV versus Ag/AgCl, in solutions containing AA and UA. Values in the order of 10 6 L mol −1 s −1 were obtained for the kinetic constant k cat for the catalytic oxidation of AA, upon evaluation by cyclic voltammetry, chronoamperometry and RDE. Furthermore, the sensor provided limits of detection of 0.19 μmol L −1 and 0.31 μmol L −1 for AA and UA, respectively. The sensor was applied for the simultaneous determination of AA and UA in urine samples and the average recoveries for these samples were 99.9 (±2.5)% and 99.9 (±2.6)%, respectively.
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paper_title: Surface modification of neural recording electrodes with conducting polymer/biomolecule blends

paper_content:

The interface between micromachined neural microelectrodes and neural tissue plays an important role in chronic in vivo recording. Electrochemical polymerization was used to optimize the surface of the metal electrode sites. Electrically conductive polymers (polypyrrole) combined with biomolecules having cell adhesion functionality were deposited with great precision onto microelectrode sites of neural probes. The biomolecules used were a silk-like polymer having fibronectin fragments (SLPF) and nonapeptide CDPGYIGSR. The existence of protein polymers and peptides in the coatings was confirmed by reflective microfocusing Fourier transform infrared spectroscopy (FTIR). The morphology of the coating was rough and fuzzy, providing a high density of bioactive sites for interaction with neural cells. This high interfacial area also helped to lower the impedance of the electrode site and, consequently, to improve the signal transport. Impedance spectroscopy showed a lowered magnitude and phase of impedance around the biologically relevant frequency of 1 kHz. Cyclic voltammetry demonstrated the intrinsic redox reaction of the doped polypyrrole and the increased charge capacity of the coated electrodes. Rat glial cells and human neuroblastoma cells were seeded and cultured on neural probes with coated and uncoated electrodes. Glial cells appeared to attach better to polypyrrole/SLPF-coated electrodes than to uncoated gold electrodes. Neuroblastoma cells grew preferentially on and around the polypyrrole/CDPGYIGSR-coated electrode sites while the polypyrrole/CH3COO−-coated sites on the same probe did not show a preferential attraction to the cells. These results indicate that we can adjust the chemical composition, morphology, electronic transport, and bioactivity of polymer coatings on electrode surfaces on a multichannel micromachined neural probe by controlling electrochemical deposition conditions. © 2001 John Wiley & Sons, Inc. J Biomed Mater Res 56: 261–272, 2001
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paper_title: Dopamine sensor based on a glassy carbon electrode modified with a reduced graphene oxide and palladium nanoparticles composite

paper_content:

We report on a sensitive electrochemical sensor for dopamine (DA) based on a glassy carbon electrode that was modified with a nanocomposite containing electrochemically reduced graphene oxide (RGO) and palladium nanoparticles (Pd-NPs). The composite was characterized by scanning electron microscopy, energy dispersive spectroscopy, and electrochemical impendence spectroscopy. The electrode can oxidize DA at lower potential (234 mV vs Ag/AgCl) than electrodes modified with RGO or Pd-NPs only. The response of the sensor to DA is linear in the 1–150 μM concentration range, and the detection limit is 0.233 μM. The sensor was applied to the determination of DA in commercial DA injection solutions.
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paper_title: Au-nanoclusters incorporated 3-amino-5-mercapto-1,2,4-triazole film modified electrode for the simultaneous determination of ascorbic acid, dopamine, uric acid and nitrite.

paper_content:

A novel biosensor has been constructed by the electrodeposition of Au-nanoclusters (nano-Au) on poly(3-amino-5-mercapto-1,2,4-triazole) (p-TA) film modified glassy carbon electrode (GCE) and employed for the simultaneous determination of dopamine (DA), ascorbic acid (AA), uric acid (UA) and nitrite (NO(2)(-)). NH(2) and SH groups exposed to the p-TA layer are helpful for the electrodeposition of nano-Au. The combination of nano-Au and p-TA endow the biosensor with large surface area, good biological compatibility, electricity and stability, high selectivity and sensitivity and flexible and controllable electrodeposition process. In the fourfold co-existence system, the linear calibration plots for AA, DA, UA and NO(2)(-) were obtained over the range of 2.1-50.1 μM, 0.6-340.0 μM, 1.6-110.0 μM and 15.9-277.0 μM with detection limits of 1.1×10(-6) M, 5.0×10(-8) M, 8.0×10(-8) M and 8.9×10(-7) M, respectively. In addition, the modified biosensor was applied to the determination of AA, DA, UA and NO(2)(-) in urine and serum samples by using standard adding method with satisfactory results.
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paper_title: Unsupported platinum nanoparticles as effective sensors of neurotransmitters and possible drug curriers

paper_content:

Abstract Herein, surface-enhanced Raman scattering (SERS) activity of positively charged unsupported platinum nanoparticles (PtNPs) with ∼12 nm size and narrow size distribution, in an aqueous solution, towards neurotransmitters was monitored at 785 nm excitation wavelength. The pure PtNPs were synthetized by polyol method. Their morphology and structure were checked by scanning electron microscopy (SEM) and X-ray diffraction spectroscopy (XRD) measurements. As a neurotransmitter bombesin (BN), which exhibits autocrine effect on the growth of normal and tumour tissues, and its fragments from the C -terminal end: BN 13−14 , BN 12−14 , BN 11−14 , BN 10−14 , BN 9−14 , and BN 8−14 (X-14 fragments of the BN amino acid sequence) were chosen. The collected spectra were interpreted and discussed. This is to determine the adsorption mode of bombesin onto the PtNPs surface and changes in this mode as a result of the bombesin backbone shortening from the N -terminal end. This is important from the point of using PtNPs as potential BN carrier into the cancerous tissue and antitumor drug.
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paper_title: Facile synthesis of nitrogen-doped graphene aerogels for electrochemical detection of dopamine

paper_content:

Abstract Nitrogen-doped graphene aerogels with three-dimensional network structures are fabricated using hydrothermal method which includes the reduction of graphene oxide by organic amine and self-assembly of reduced graphene oxide. The effect of amine-containing compounds including aniline, 2-aminoethanol, ethylenediamine, melamine and chitosan on the assembly of nitrogen-doped graphene aerogel is investigated. The microstructure and chemical composition of nitrogen-doped graphene aerogels are characterized. The results reveal that nitrogen-doped graphene aerogel prepared using aniline as nitrogen source possesses a large specific surface area, high nitrogen content, good mechanical strength and excellent electrical conductivity. Based on these features, the as-prepared nitrogen-doped graphene aerogel shows high performance in electrochemical detection of dopamine in the presence of uric acid and ascorbic acid. Given the facile and scalable processability of aerogels, the proposed nitrogen-doped graphene aerogels are expected to have potential applications in sensors and other related devices.
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paper_title: Highly selective dopamine electrochemical sensor based on electrochemically pretreated graphite and nafion composite modified screen printed carbon electrode

paper_content:

Abstract Herein, we report a highly selective dopamine electrochemical sensor based on electrochemically pretreated graphite/nafion composite modified screen printed carbon (SPC) electrode. Electrochemically activated graphite/nafion composite was prepared by using a simple electrochemical method. Scanning electron microscope (SEM) used to characterize the surface morphology of the fabricated composite electrode. The SEM result clearly indicates that the graphitic basal planes were totally disturbed and leads to the formation of graphite nanosheets. The composite modified electrode showed an enhanced electrocatalytic activity toward the oxidation of DA when compared with either electrochemical pretreated graphite or nafion SPC electrodes. The fabricated composite electrode exhibits a good electrocatalytic oxidation toward DA in the linear response range from 0.5 to 70 μM with the detection limit of 0.023 μM. The proposed sensor also exhibits very good selectivity and stability, with the appreciable sensitivity. In addition, the proposed sensor showed satisfactory recovery results toward the commercial pharmaceutical DA samples.
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paper_title: Formation of novel polymeric films derived from 4-hydroxybenzoic acid

paper_content:

Abstract This work reports electrochemical and morphological studies of formation of poly(4-hydroxybenzoic acid), prepared in different pH, on the graphite surface. Cyclic voltammetry, electrochemical impedance spectroscopy (EIS), electrochemical quartz crystal microbalance (EQCM) and atomic force microscopy (AFM) have been carried out to study the modified electrodes formed. The electrodes modified with poly(4-HBA), prepared in pH 0.5 and 7.0, presented oxidation/reduction peaks, but no peak was detected to modified electrodes prepared in pH 12.0. Voltammetric studies showed decrease in oxidation/reduction currents and slower electron transport across the polymer for all pH values, however, the electron transport was higher when the polymer was prepared in acid medium. EIS analysis indicated that the charge transfer resistance for poly(4-HBA) electropolymerized at pH 12.0 was about 2 and 1.4 times higher when compared to pH 0.5 and 7.0, respectively. Studies through EQCM showed higher amount of polymer mass deposited in acid medium. Images by AFM indicated that the topography is affected by pH value, whereas films prepared in acidic pH conditions presented higher roughness.
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paper_title: Carbon nanomaterial based electrochemical sensors for biogenic amines

paper_content:

This review describes recent advances in the use of carbon nanomaterials for electroanalytical detection of biogenic amines (BAs). It starts with a short introduction into carbon nanomaterials such as carbon nanotubes, graphene, nanodiamonds, carbon nanofibers, fullerenes, and their composites. Next, electrochemical sensing schemes are discussed for various BAs including dopamine, serotonin, epinephrine, norepinephrine, tyramine, histamine and putrescine. Examples are then given for methods for simultaneous detection of various BAs. Finally, we discuss the current and future challenges of carbon nanomaterial-based electrochemical sensors for BAs. The review contains 175 references.
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paper_title: Interactions of graphene derivatives with glutamate-neurotransmitter: A parallel first principles - Docking investigation

paper_content:

Abstract Glutamate plays an important role in excitatory neurotransmission, learning, and memory processes, and under pathological conditions it is directly associated with several chronic neurological disorders, such as depression, epilepsy, schizophrenia, and Parkinson's. Therefore, the detection and quantification of Glutamate is important for the rapid diagnosis of these diseases. Using first principles and molecular docking simulations we have evaluated the energetic, structural, and binding properties of graphene derivatives, such as pristine graphene (pristine-Gr) and oxidized graphene with carboxylic (Gr-COOH), carbonyl (Gr-COH), hydroxyl (Gr-OH), and epoxy (-O-) groups interacting with the glutamate neurotransmitter. The calculated binding affinity free energies from the docking complexes (glutamate-graphene family) suggest higher oxidized graphene-based glutamate molecular recognition than the pristine-Gr, with the following order of oxidized graphene derivatives according to ab initio results: (Gr-O∼Gr-COOH ∼ Gr-COH > Gr-OH)>pristine-Gr. Herein, the ab initio binding energies found for the glutamate-graphene family complexes are in the range of 0.24–0.80 eV. The configurations studied showed a biophysical adsorption regime without significant changes in the physico-chemical properties of the adsorbed glutamate neurotransmitter, in accordance with the general acceptance criteria of the detection systems.
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paper_title: Conducting polymer nanostructures and their application in biosensors.

paper_content:

Nowadays, functionalized conducting polymer nanomaterials have been received great attention in nanoscience and nanotechnology because of their large surface area. This article reviews various methods for synthesis of conducting polymer nanostructures and their applications in sensing materials, focusing on hard-template, soft-template and other methods and the formation mechanism of conducting polymer nanostructures by these methods. Conducting polymer nanostructures, such as nanotubes, nanowires, and nanoparticles, as sensing platforms for various applications are also summarized.
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paper_title: Conducting polymer-based electrochemical biosensors for neurotransmitters: A review

paper_content:

Abstract Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.
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paper_title: Modified fluorine-doped tin oxide electrode with inorganic ruthenium red dye-multiwalled carbon nanotubes for simultaneous determination of a dopamine, uric acid, and tryptophan

paper_content:

Abstract For the first time, a modified F-doped SnO 2 electrode with ruthenium red (RuRe) inorganic dye immobilized on a multi-walled carbon nanotube was been developed. The RuRe maintained high activity on this nanomaterial, catalyzing the oxidation of dopamine (DA), uric acid (UA) and tryptophan (Trp) in a simultaneous determination, which was electrochemically reduced at 0.377, 0.552 and 0.841 V versus SCE on the biosensor surface. The measurements were carried out using cyclic voltammetry in phosphate buffer solution with pH 3.0. Under optimum conditions, the biosensor showed linear response up to 283 μM for DA and 433 μM for UA and Trp with limit of detection 0.15, 0.14 and 0.14 μM for DA, UA and Trp, respectively. The analytical performance of this sensor has been evaluated for simultaneous detection of DA, UA and Trp in human serum and urine samples.
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paper_title: Electrochemical detection of serotonin based on a poly(bromocresol green) film and Fe3O4nanoparticles in a chitosan matrix

paper_content:

A composite film containing poly(bromocresol green), magnetic nanoparticles and multiwalled carbon nanotubes was fabricated for the sensitive determination of serotonin. The poly(bromocresol green) was prepared by electropolymerization on a glassy carbon electrode surface, then the multiwalled carbon nanotubes and magnetic nanoparticles in a chitosan matrix were dropped onto the surface of the poly(bromocresol green) film. The modified electrode displayed an enhanced differential pulse voltammetric response to serotonin in the presence of dopamine. Its peak current (at an oxidation voltage of 0.36 V vs. Ag/AgCl) increased linearly in the serotonin concentration range 0.5–100 μM with a detection limit of 80 nM (at an S/N of 3). The sensor was highly sensitive and stable. It was applied to the direct determination of serotonin spiked into human serum samples. These results show that the nanocomposite films are good modifying materials for use in the fabrication of electrochemical sensors.
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paper_title: A polyaniline–zeolite nanocomposite material based acetylcholinesterase biosensor for the sensitive detection of acetylcholine and organophosphates

paper_content:

In this work, a nanoporous polyaniline–nanocrystalline zeolite organic–inorganic hybrid material was synthesized. An acetylcholinesterase electrochemical biosensor based on a polyaniline–zeolite nanocomposite material was fabricated for the sensitive detection of neurotransmitter acetylcholine and the resultant biosensor was further employed for the detection of toxic organophosphate pesticides. The results demonstrate that the polyaniline–nanocrystalline zeolite based acetylcholinesterase biosensor exhibited much higher activity when compared to conventional polyaniline. The nanoporous polyaniline–nanocrystalline zeolite based biosensor exhibited good stability, sensitivity, linear range, and limit of detection. The analytical performance of the developed biosensor was demonstrated in the determination of these pesticides in different real samples (apple, cabbage, tap water, and river water) with satisfactory recovery.
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paper_title: Low-cost screen-printed electrodes based on electrochemically reduced graphene oxide-carbon black nanocomposites for dopamine, epinephrine and paracetamol detection

paper_content:

A green approach for the preparation of carbon black (CB) and electrochemically reduced graphene oxide composite (ERGO) is described based on screen printed carbon electrodes (SPCEs) fabricated on poly(ethylene terephthalate) (PET) as electrochemical sensors. This approach leads to a heterogeneous hydrophilic surface with high concentration of defect sites according to scanning electron microscopy, contact angle and Raman spectroscopy measurements. The SPCE/CB-ERGO sensor was tested with dopamine (DA), epinephrine (EP) and paracetamol (PCM), exhibiting an enhanced electrocatalytic performance compared to the bare SPCE. It displayed a wider linear range, lower limit of detection and a remarkably higher analytical sensitivity, viz. 1.5, 0.13 and 0.028 A L mol-1 for DA, EP and PCM, respectively, being also capable of simultaneous determination of the three analytes. Such high performance is demonstration that SPCE/CB-ERGO may serve as generic platform for cost-effective flexible electrochemical sensors.
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paper_title: Nanocomposites based on carbon nanotubes and redox-active polymers synthesized in a deep eutectic solvent as a new electrochemical sensing platform

paper_content:

The redox polymer poly(methylene blue) was synthesized by electropolymerization in ethaline deep eutectic solvent (PMBDES), and employed in a new nanostructured composite together with carbon nanotubes (CNT). The polymer was formed either before or after CNT deposition on glassy carbon electrodes (GCE) to obtain GCE/PMBDES/CNT and GCE/CNT/PMBDES modified electrodes, respectively. The morphology of the hybrid films was investigated by scanning electron microscopy, and their electrochemical performance by cyclic voltammetry and electrochemical impedance spectroscopy. The composite with the highest faradaic response and electronic conductivity was identified and applied as a platform for the determination of ascorbic acid by fixed potential amperometry at +0.2 V vs. Ag/AgCl, and acetaminophen by square wave voltammetry and differential pulse voltammetry at +0.67 V vs. Ag/AgCl. The limits of detection of the best sensor configurations are 1.7 μM for AA, and 1.6 μM for APAP, and respective electrochemical sensitivities are 2.2 μA cm-2 μM−1 and 68.7 μA cm-2μ​M-1. The applicability of the electrochemical sensors was demonstrated by the successful quantification of both these key analytes in complex pharmaceutical formulations.
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paper_title: The Rise of Organic Bioelectronics

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In this Perspective, we make the case that the biological applications of organic semiconductor devices are significant. Indeed, we argue that this is an arena where organic materials have an advantage compared to traditional electronic materials, such as silicon. By discussing the physical structure and morphology of conjugated polymers, we are able to emphasize the key properties that make organic materials ideal for bioelectronics applications. We highlight a few recent devices that show either unique features or exceptionally high performance. On the basis of these examples, we discuss the future trajectory of this emerging field, note areas where further research is needed, and suggest possible applications in the short term.
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paper_title: An electrochemical sensor for detection of neurotransmitter-acetylcholine using metal nanoparticles, 2D material and conducting polymer modified electrode.

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An essential biological sensor for acetylcholine (ACh) detection is constructed by immobilizing enzymes, acetylcholinesterase (AChE) and choline oxidase (ChO), on the surface of iron oxide nanoparticles (Fe2O3NPs), poly(3,4-ethylenedioxythiophene) (PEDOT)-reduced graphene oxide (rGO) nanocomposite modified fluorine doped tin oxide (FTO). The qualitative and quantitative measurements of nanocomposites properties were accomplished by scanning electron microscope (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). This prepared biological sensor delineated a wide linear range of 4.0nM to 800μM with a response time less than 4s and detection limit (based on S/N ratio) of 4.0nM. The sensor showed perfect sensitivity, excessive selectivity and stability for longer period of time during storage. Besides its very high-sensitivity, the biosensor has displayed a low detection limit which is reported for the first time in comparison to previously reported ACh sensors. By fabricating Fe2O3NPs/rGO/PEDOT modified FTO electrode for determining ACh level in serum samples, the applicability of biosensor has increased immensely as the detection of the level neurotransmitter is first priority for patients suffering from memory loss or Alzheimer's disease (AD).
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paper_title: Stretched graphene tented by polycaprolactone and polypyrrole net–bracket for neurotransmitter detection

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Abstract A net-bracket built out from the core@shell structure of chemically oxidized polypyrrole (PPy) coated electrospun polycaprolactone (PCL) nanofibers, and the following surface modification of a thin layer of positively charged poly(dimethyl diallyl ammonium chloride) (PDDA) has been applied for stretching the reduced graphene oxide (RGO) sheets to some extent with the electrochemical deposition method. The as-formed RGO/PDDA/PCL@PPy nanocomposites were investigated by using scanning electron microscopy, transmission electron microscope, X-ray diffraction and Raman spectroscopy. The graphene tented by the net-bracket showed remarkable electrocatalytic properties in detecting the neurotransmitter dopamine (DA). Low detection limit of 0.34 μM (S/N = 3) with the wide linear detection range from 4 μM to 690 μM was obtained. The successful determination of DA in real urine samples and DA injection were achieved. Such attractive fabrication strategy can be extended to make other graphene sheet-based sensors.
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paper_title: Electroanalysis of neurotransmitters via 3D gold nanoparticles and a graphene composite coupled with a microdialysis device

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Abstract We developed a novel biosensor, which used the uniform graphene oxide (GO) to afford gold nanoparticles (GNPs). The advantages of this biosensor are the better sensitivities not only of GO but also the GNPs fabricated on it for neurotransmitters, especially the lower cost in biosensor modification. The modified composite was characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDS) and electrochemical methods. The determination conditions were optimized and the peak currents of DA and 5‑HT were linear, with the concentrations in the range of 9.0 × 10−7 to 7.0 × 10−5 M for DA, and 6.0 × 10−7 to 4.0 × 10−5 M for 5‑HT. The detection limits were 7.0 × 10−9 M for 5‑HT and 5.6 × 10−8 M for DA. A micro-capacity electrolytic cell was designed using the modified biosensor to connect to the microdialysis device and it was successfully applied to determine the concentrations of DA and 5‑HT in the samples, with a spiked recovery of 82.0–118%.
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paper_title: Bio-inspired fish robot based on chemical sensors

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Abstract In this study, we designed bio-inspired fish robot capable of swimming according to the directives sent in form of chemical messengers. The concentration of hydrogen ions in the environment was detected by electro-chemical multi-sensors platform. The acquired signal was then transformed into electronic signal to be used in robot control electronics. The pH sensors were realized by polyaniline (PANI) film electrochemically deposited on the graphite screen-printed electrode surface. The electrochemical characteristics of the modified sensors were studied using electrochemical and microscopic techniques. Experiments on PANI-modified sensors in order to obtain the best sensitivity as chemical sensing used in fish robot were carried out. Finally, preliminary experiments were performed using pH sensors to control fish robot’s tail movement. The realized robotic platform is considered as a proof-of-concept for the development of multi-sensors fish robot that can be used for water monitoring and warning tool in fish farms.
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paper_title: Applications of conducting polymer composites to electrochemical sensors: A review

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Abstract Conducting polymers (CPs) constitute an important class of organic functional materials. Their unique physical and electrical properties and being inexpensive, easy to synthesize, and suitable matrices for biomolecule immobilization have enabled them to find a wide range of use, including playing roles in supercapacitors, batteries, electrochromic devices, solar cells, sensors, and biomedical applications. To enhance the performance of the CPs, various composite materials have been synthesized with carbon-based materials, metals or metal oxides, etc. This review comprehensively discusses CPs and their composites, followed by their applications. The purpose of this review is to summarize the electrochemical sensors that are based on CPs and their composites and to address future aspects of electrochemical sensing materials.
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paper_title: A selective voltammetric detection for dopamine using poly (gallic acid) film modified electrode

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Abstract The electrochemistry behavior of dopamine was investigated by cyclic voltammetry and differential pulse voltammetry at a poly (gallic acid) film modified glassy carbon electrode. Two electrons and two protons participated in the diffusion-controlled electrocatalytic oxidation of dopamine with a diffusion coefficient of 2.186 × 10 −5 cm 2 /s. The interference of ascorbic acid with the determination of dopamine could be efficiently eliminated. This work provided a simple approach to selectively and sensitively detect dopamine in the presence of high concentration of ascorbic acid.
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paper_title: Electrochemical sensors and biosensors based on redox polymer/carbon nanotube modified electrodes: a review.

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Abstract The aim of this review is to present the contributions to the development of electrochemical sensors and biosensors based on polyphenazine or polytriphenylmethane redox polymers together with carbon nanotubes (CNT) during recent years. Phenazine polymers have been widely used in analytical applications due to their inherent charge transport properties and electrocatalytic effects. At the same time, since the first report on a CNT-based sensor, their application in the electroanalytical chemistry field has demonstrated that the unique structure and properties of CNT are ideal for the design of electrochemical (bio)sensors. We describe here that the specific combination of phenazine/triphenylmethane polymers with CNT leads to an improved performance of the resulting sensing devices, because of their complementary electrical, electrochemical and mechanical properties, and also due to synergistic effects. The preparation of polymer/CNT modified electrodes will be presented together with their electrochemical and surface characterization, with emphasis on the contribution of each component on the overall properties of the modified electrodes. Their importance in analytical chemistry is demonstrated by the numerous applications based on polymer/CNT-driven electrocatalytic effects, and their analytical performance as (bio) sensors is discussed.
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paper_title: Hyphenation of enzyme/graphene oxide-ionic liquid/glassy carbon biosensors with anodic differential pulse stripping voltammetry for reliable determination of choline and acetylcholine in human serum

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Abstract Acetylcholine (ACh) and its precursor choline (Ch) play important roles in many biological processes. It is expected that Alzheimer's disease is occurred due to the reduction in synthesis of ACh. On the other hand, the increase in the level of ACh results in a depression of heart rate and over production of saliva. Therefore, the quantitative determination of Ch and ACh is very important in biological media. In the current work, sensitive and selective biosensors composed of choline oxidase (ChO) and/or acetylcholine esterase (AChE) on graphene oxide-ionic liquid (GO-IL)/ glassy carbon electrode (GCE) hyphenated with anodic differential pulse stripping voltammetry (ADPSV) were firstly established for the determination of ACh and Ch in human serum samples. The molecular bond of ionic liquid 1-allyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (AMIM TFSI) with GO was investigated by FT-IR and UV–Vis techniques. Furthermore, the surface topography of ChO/GO–IL and AChE-ChO/GO–IL composites was investigated by SEM and XRD. Then, the electron transfer features of biosensors ChO/GO-IL/GCE and AChE-ChO/GO-IL/GCE were characterized by the electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. The ADPSV was further used for the determination of Ch and ACh. The experimental parameters such as differential pulse working potential, differential pulse scan rate, equilibrium time and long-term stability were further optimized. Detection limits of 0.885 and 1.352 nmol L−1 with excellent linearity (R2 = 0.9996) over the range of 5–1000 nmol L−1 were obtained for Ch and ACh, respectively. The developed analytical methods showed excellent accuracy and precision for the determination of Ch and ACh in human serum samples avoiding their pretreatment or purification.
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paper_title: Determination of some neurotransmitters at cyclodextrin/ionic liquid crystal/graphene composite electrode

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A novel reduced graphene oxide (RGO) composite glassy carbon electrode modified with ionic liquid crystal (ILC), 1-Butyl-1-methylpiperidinium hexa-fluoro-phosphate and cyclodextrin (CD/ILC/RGO/ILC/GC) was fabricated via mechanical casting of each layer. The modified electrode was used for the determination of some neurotransmitters such as dopamine (DA), epinephrine (EP), norepinephrine (NEP), levodopa (L-DOPA), 3,4-dihydroxy-phenyl acetic acid (DOPAC) and serotonin (ST). This electrode anticipated the good electron mobility and large surface area of graphene, high ionic conductivity and stability of ionic liquid crystal besides the pre-concentrating effect of CD. Optimization of the sensor performance is presented and resulted in a better current signal. The linear dynamic range of the modified electrode was from 0.8×10−7–0.1×10−4 mol L−1 for determination of EP with a correlation coefficient 0.998 and LOD 0.0117×10−9 mol L−1. The sensor was sensitive and successfully applied for direct determination of EP in human urine samples with good recovery results.
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paper_title: Strategies for enhancing the analytical performance of nanomaterial-based sensors

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We provide a state-of-the-art review of the main strategies for the enhancement of analytical performance of sensors using nanomaterials, particularly nanowires and carbon-based materials. We emphasize the way to overcome the problem of device-to-device variation. We discuss the study of the influence of nanomaterial characteristics, sensor dimensions and operational conditions on sensing performance, and the application of appropriate calibration models.
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paper_title: Boron-doped multi-walled carbon nanotubes as sensing material for analysis of dopamine and epinephrine in presence of uric acid

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Abstract Boron-doped multi-walled carbon nanotubes (B-MWCNTs) were synthesized, treated with hydrochloric acid, “piranha” solution, and decorated with gold nanoparticles (AuNPs). B-MWCNTs were characterized using Raman spectroscopy, scanning electron- and transmission electron microscopy, and electrochemical techniques. The results exhibit enhanced response and sensitivity of B-MWCNTs upon modification with AuNPs. Analysis of dopamine (DA) and epinephrine (EP) in presence of uric acid (UA) was investigated on B-MWCNTs/AuNPs in pig blood serum. Limits of detection of 0.20 and 0.30 μM were estimated for DA and EP, respectively. The findings demonstrate that B-MWCNTs/AuNPs is proper for analysis of DA and EP under coexistence of UA.
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paper_title: Molecular modeling study on the possible polymers formed during the electropolymerization of 3-hydroxyphenylacetic acid.

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The compound 3-hydroxyphenylacetic acid (3-HPA) has been used as a monomer in the synthesis of polymeric films by electropolymerization; these films serve as supports for the immobilization of biomolecules in electrochemical biosensors. To assist in the elucidation of the mechanism of 3-HPA electropolymerization, a systematic quantum mechanical study was conducted. In addition to the monomer, all possible intermediates and the probable oligomers formed during the electropolymerization were investigated using a density functional theory (DFT) method combined with a previous conformational analysis performed with the aid of the RM1 semi-empirical method or a Monte Carlo conformational analysis with the force field OPLS-2005. From the data analysis combined with the experimental results, a mechanism was proposed for the main route of formation of the polymeric films. The mechanism involves the formation of polyethers from the coupling of phenoxide radicals and radicals based on the aromatic ring.
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paper_title: Nanostructured photoactivatable electrode surface based on pyrene diazirine

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Abstract An original versatile methodology for molecular grafting on different surfaces via the photoinduced formation of a covalent bond based on a diazirine group is reported. The synthesis and electrochemical behavior of a new diazirine derivative which acts as a molecular linking bridge bearing both a photoactivatable covalent binding group (diazirine) and a non-covalent binding group (pyrene) is described. The resulting pyrene-diazirine was electropolymerized onto a platinum electrode and under UV irradiation was successfully used to graft ferrocenemethanol and glucose oxidase (model small molecule and protein, respectively), conferring specific properties on the resulting materials. Furthermore, the immobilization of the diazirine derivative onto multi-walled carbon nanotubes (MWCNT) by π-stacking interaction or by electropolymerization onto both bare and MWCNT-coated platinum electrodes enabled photografting of glucose oxidase.
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paper_title: Fast and Selective Plasmonic Serotonin Detection with Aptamer-Gold Nanoparticle Conjugates

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Neurotransmitters detection is critical to understanding communication between the brain and peripheral tissue. Serotonin is a key neurotransmitter linked to a number of conditions, but a full understanding of its role in disease is still lacking. The development of fast and selective serotonin detection platforms will provide researchers with tools to monitor serotonin in individuals before and after treatment for the condition of interest. Aptamer-gold nanoparticles conjugates that responded colorimetrically to serotonin with minimal response to its metabolite and other neurotransmitters were designed by simply adsorbing the DNA on the surface of AuNPs. A plasmonic assay for serotonin detection was designed with a response to biologically relevant serotonin levels. Importantly, the assay performance was not compromised when tested in filtered spiked fetal bovine serum as a mimic of biofluids. This work shows that these simple and stable Apt-AuNP conjugates are promising tools to develop fast assays for point-of-care and personalized diagnostics applications.
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paper_title: Advanced biomedical applications of carbon nanotube.

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Abstract With advances in nanotechnology, the applications of nanomaterial are developing widely and greatly. The characteristic properties of carbon nanotubes (CNTs) make them the most selective candidate for various multi-functional applications. The greater surface area of the CNTs in addition to the capability to manipulate the surfaces and dimensions has provided greater potential for this nanomaterial. The CNTs possess greater potential for applications in biomedicine due to their vital electrical, chemical, thermal, and mechanical properties. The unique properties of CNT are exploited for numerous applications in the biomedical field. They are useful in both therapeutic and diagnostic applications. They form novel carrier systems which are also capable of site-specific delivery of therapeutic agents. In addition, CNTs are of potential application in biosensing. Many recently reported advanced systems of CNT could be exploited for their immense potential in biomedicine in the future.
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paper_title: Overview and recent advances in electrochemical sensing of glutathione – A review

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Abstract The present paper is aimed at providing an overview of the recent advances in the electrochemical sensing of glutathione (GSH), an important electrochemically and biologically active molecule, for the period 2012–2018. Herein, the analytical performances of newly developed electrochemical methods, procedures and protocols for GSH sensing are comprehensively and critically discussed with respect to the type of method, electrodes used (new electrode modifications, advanced materials and formats), sample matrices, and basic validation parameters obtained (limit of detection, linear dynamic range, precision, selectivity/evaluation of interferences). This paper considers electrochemical methods used alone as well as the hyphenated methods with electrochemical detection (ECD), such as HPLC-ECD or CE-ECD. The practical applicability of the platforms developed for GSH detection and quantification is mostly focused on pharmaceutical and biomedical analysis. The most significant electrochemical approaches for GSH detection in multicomponent analyte samples and multicomponent matrices and for real-time in vivo GSH analysis are highlighted. The great variability in the electrochemical techniques, electrode approaches, and obtainable performance parameters, discussed in this review, brought new insights not only on current GSH and glutathione disulfide (GSSG) determinations, but, along with this, on the advances in electrochemical analysis from a more general point of view.
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paper_title: Nanostructured electropolymerized poly(methylene blue) films from deep eutectic solvents. Optimization and characterization

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Abstract Electropolymerization in deep eutectic solvents (DES) as a new class of “green” solvents, was employed to prepare poly(methylene blue) (PMB) polymers with different nanostructured morphologies. PMB films were synthesized on glassy carbon electrodes by potential cycling from a mixture of 90% ethaline (choline chloride: ethylene glycol) and 10% aqueous solution with different ionic composition, i.e. Na + , SO 4 2− , ClO 4 − , NO 3 − , Cl − . The scan rate during polymerization was the key parameter in controlling film structure, confirmed by scanning electron microscopy. Electrochemical characterization of the polymers demonstrated differences in the electrochemical voltammetric and impedance properties of all synthesized PMB films. The PMB film obtained at 150 mV s −1 polymerisation scan rate with stirring, formed nanostructured ordered and granular films, was shown to have superior electrochemical properties. Electrochemical quartz crystal microbalance gravimetry was used to quantify the amount of deposited film and probe the polymerization mechanism. PMB film modified electrodes obtained in optimized DES media at different scan rates were tested for ascorbate sensing, in order to establish the most suitable PMB DES film for (bio)sensing applications.
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paper_title: Methylene Blue/Multiwall Carbon Nanotube Modified Electrode for the Amperometric Determination of Hydrogen Peroxide

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A novel amperometric sensor based on the incorporation of multiwalled carbon nanotubes (MWCNT) into a poly(methylene blue) (PMB) film immobilized on carbon composite electrodes is described. Cyclic voltammetry indicated that at a surface covered by a MWCNT/PMB layer the cathodic reduction of hydrogen peroxide is facilitated and occurs already at 0.0 V versus SCE. The effect of the order of deposition of PMB and MWCNT, as well as its loading, on electrochemical behaviour was evaluated by cyclic voltammetry and electrochemical impedance spectroscopy. The influence of the various immobilised platforms on the electrocatalytic performance towards hydrogen peroxide was also examined.
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paper_title: Recent Advances in the Detection of Neurotransmitters

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Neurotransmitters are chemicals that act as messengers in the synaptic transmission process. They are essential for human health and any imbalance in their activities can cause serious mental disorders such as Parkinson’s disease, schizophrenia, and Alzheimer’s disease. Hence, monitoring the concentrations of various neurotransmitters is of great importance in studying and diagnosing such mental illnesses. Recently, many researchers have explored the use of unique materials for developing biosensors for both in vivo and ex vivo neurotransmitter detection. A combination of nanomaterials, polymers, and biomolecules were incorporated to implement such sensor devices. For in vivo detection, electrochemical sensing has been commonly applied, with fast-scan cyclic voltammetry being the most promising technique to date, due to the advantages such as easy miniaturization, simple device architecture, and high sensitivity. However, the main challenges for in vivo electrochemical neurotransmitter sensors are limited target selectivity, large background signal and noise, and device fouling and degradation over time. Therefore, achieving simultaneous detection of multiple neurotransmitters in real time with long-term stability remains the focus of research. The purpose of this review paper is to summarize the recently developed sensing techniques with the focus on neurotransmitters as the target analyte, and to discuss the outlook of simultaneous detection of multiple neurotransmitter species. This paper is organized as follows: firstly, the common materials used for developing neurotransmitter sensors are discussed. Secondly, several sensor surface modification approaches to enhance sensing performance are reviewed. Finally, we discuss recent developments in the simultaneous detection capability of multiple neurotransmitters.
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paper_title: Selective Detection of Dopamine Combining Multilayers of Conducting Polymers with Gold Nanoparticles

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Electrodes based on the combination of three-layered films formed by two different conducting polymers and gold nanoparticles have been developed for the selective voltammetric determination of dopamine in mixtures with ascorbic acid and uric acid and human urine samples with real interferents. Voltammetric studies of solution mixtures indicate that electrodes formed by alternated layers of poly(3,4-ethylenedioxithiophene) (internal and external layer) and poly(N-methylpyrrole) (intermediate layer) show the best performance in terms of sensitivity and resolution. Furthermore, the sensitivity of such three-layered electrodes increases only slightly after coating its surface with gold nanoparticles (AuNPs), indicating that the catalytic effect typically played by AuNPs in the oxidation of dopamine is less effective in this case. Electrochemical pretreatments based on the application of consecutive oxidation-reduction cycles to electrodes before the detection process have been found to improve the selectivity without altering the sensitivity. On the other hand, the flux of dopamine to the three-layered surface increases linearly with the scan rate. The detection limit for these electrodes is around 10 μM DA in mixtures with uric acid, ascorbic acid, and cetaminophen, decreasing to 2-3 μM in the absence of such interferents. The utility of three-layered electrodes as sensors has also been demonstrated by determining DA in human samples with real interferents.
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paper_title: Role of conducting polymer and metal oxide-based hybrids for applications in ampereometric sensors and biosensors

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Abstract In recent years, the electrochemical sensors are used extensively due to their unique properties, especially in the biomedical research. Conducting polymers are well known for their inbuilt charge transfer properties and biocompatibility. Modification of conducting polymers using metal particles, metal oxides, and carbon materials enhance the sensitivity, stability, and reproducibility of the electrode which enhances the overall sensor performance. In this present review, we discuss recent achievements of electrochemical biosensors and sensor performance of various nanostructured conducting polymers and various metal oxides. Various synthesis methodologies of nanostructured conducting polymers and metal oxide-based hybrid sensors are also discussed. Analytical performance of nanohybrids of metal oxides incorporated with conducting polymers such as polyaniline, polypyrrole, polythiophene and their derivatives is elaborated. The characteristics of conducting polymer-based hybrids, metal oxide-based hybrids, and their application in biosensors are reviewed.
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paper_title: Fluorescent Gold Nanoclusters for Selective Detection of Dopamine in Cerebrospinal fluid

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Since the last two decades, protein conjugated fluorescent gold nanoclusters (NCs) owe much attention in the field of medical and nanobiotechnology due to their excellent photo stability characteristics. In this paper, we reported stable, nontoxic and red fluorescent emission BSA-Au NCs for selective detection of L-dopamine (DA) in cerebrospinal fluid (CSF). The evolution was probed by various instrumental techniques such as UV-vis spectroscopy, High resolution transmission electron microscopy (HTEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), photoluminescence spectroscopy (PL). The synthesised BSA-Au NCs were showing 4-6 nm with high fluorescent ~8% Quantum yield (QY). The fluorescence intensity of BSA-Au NCs was quenched upon the addition of various concentrations of DA via an electron transfer mechanism. The decrease in BSA-Au NCs fluorescence intensity made it possible to determine DA in PBS buffer and the spiked DA in CSF in the linear range from 0 to 10 nM with the limit of detection (LOD) 0.622 and 0.830 nM respectively. Best of our knowledge, as-prepared BSA-Au NCs will gain possible strategy and good platform for biosensor, drug discovery, and rapid disease diagnosis such as Parkinson's and Alzheimer diseases.
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paper_title: Electrogeneration and characterization of photoactivable films and their application for enzyme grafting

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Abstract New benzophenone derivatives functionalized by electropolymerizable pyrrole, vinylaniline and indole groups have been synthesized and electrochemically characterized. Upon electrochemical polymerization in acetonitrile, only two photoactivable polypyrrole films were prepared. Although the latter differed in the length of the spacer bridging benzophenone and pyrrole groups, similar photografting properties were obtained under irradiation leading to the anchoring of an alkaline phosphatase monolayer. A mean surface coverage of enzyme, 622 ng cm −2 , was reached for the poly(pyrrole–benzophenone) films. The enzyme maintained 63% of its initial activity after 30 days indicating a good stability of the photografted molecule.
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paper_title: Acetamiprid multidetection by disposable electrochemical DNA aptasensor.

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In this work, we propose an electrochemical DNA aptasensor for sensitive multidetection of acetamiprid based on a competitive format and disposable screen-printed arrays. To improve the sensitivity of the aptasensor, polyaniline film and gold nanoparticles were progressively electrodeposited on the graphite screen-printed electrode surface by cyclic voltammetry. Gold nanoparticles were then employed as platform for thiol-tethered DNA aptamer immobilization. Different acetamiprid solutions containing a fixed amount of biotinylated complementary oligonucleotide sequence by DNA aptasensor arrays were analyzed. Streptavidin-alkaline phosphatase conjugate was then added to trace the affinity reaction. The enzyme catalyzed the hydrolysis of 1-naphthyl phosphate to 1-naphthol. The enzymatic product was detected by differential pulse voltammetry. A decrease of the signal was obtained when the pesticide concentration was increased, making the sensor work as signal off sensor. Under optimized conditions by testing key experimental parameters, a dose-response curve was constructed between 0.25 and 2.0µM acetamiprid concentration range and a limit of detection of 0.086µM was calculated. The selectivity of the aptasensor was also confirmed by the analysis of atrazine pesticide. Finally, preliminary experiments in fruit juice samples spiked with acetamiprid were also performed.
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paper_title: A Novel Label-Free Immunosensor Based on Activated Graphene Oxide for Acetaminophen Detection

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A simple label-free immunosensor for the selective detection of acetaminophen was developed by modifying a graphite based screen-printed electrode with graphene oxide after the functionalization with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. The template made by layer-by-layer technique provides activated carboxylic groups, which form amidic covalent bonds with the terminal amine groups from the antiacetaminophen antibody. The optimization of antibody immobilization and the blocking of the free active groups from graphene template with bovine serum albumin was performed by using electrochemical impedance spectroscopy, cyclic voltammetry and square wave voltammetry. The electrochemical quartz crystal microbalance technique was used to determine the quantity of different components deposited onto the electrode surface during the optimization steps. The above described immunosensor was applied with good results for the determination of acetaminophen in synthetic and real samples by using square wave voltammetry. A limit of detection of 0.17 µM (S/N=3) was obtained with no or minimal interference of dosage forms excipients and serum components.
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paper_title: Sensitive and selective dopamine determination in human serum with inkjet printed Nafion/MWCNT chips

paper_content:

Abstract An inkjet printed Nafion/MWCNT chip was developed for rapid dopamine determination in undiluted human serum. A well-dispersed Nafion/MWCNT composite ink was investigated with homogeneous double layers which increased the efficiency of dopamine detection, where direct electron exchange was achieved, producing a measurable current change at the underlying sensor electrode. This platform successfully demonstrated direct detection of DA concentrations (0.1 μM to 10 μM, R = 0.999) in real human serum samples using DPV and amperometry methods. This direct measurement of DA in serum samples without pretreatment and dilution is reported for the first time in a Nafion/MWCNT system.
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paper_title: Selective and efficient electrochemical biosensing of ultrathin molybdenum disulfide sheets

paper_content:

Atomically thin molybdenum disulfide (MoS2) sheets were synthesized and isolated via solvent-assisted chemical exfoliation. The charge-dependent electrochemical activities of these MoS2 sheets were studied using positively charged hexamine ruthenium (III) chloride and negatively charged ferricyanide/ferrocyanide redox probes. Ultrathin MoS2 sheet-based electrodes were employed for the electrochemical detection of an important neurotransmitter, namely dopamine (DA), in the presence of ascorbic acid (AA). MoS2 electrodes were identified as being capable of distinguishing the coexistence of the DA and the AA with an excellent stability. Moreover, the enzymatic detection of the glucose was studied by immobilizing glucose oxidase on the MoS2. This study opens enzymatic and non-enzymatic electrochemical biosensing applications of atomic MoS2 sheets, which will supplement their established electronic applications.
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paper_title: Advances in enzyme-free electrochemical sensors for hydrogen peroxide, glucose, and uric acid

paper_content:

National Basic Research Program of China [2010CB732402]; National Nature Scientific Foundation of China [21175112, 21375112, 21305050]
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paper_title: Immobilization of Ni-Pd/core-shell nanoparticles through thermal polymerization of acrylamide on glassy carbon electrode for highly stable and sensitive glutamate detection.

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The preparation of a persistently stable and sensitive biosensor is highly important for practical applications. To improve the stability and sensitivity of glutamate sensors, an electrode modified with glutamate dehydrogenase (GDH)/Ni-Pd/core-shell nanoparticles was developed using the thermal polymerization of acrylamide (AM) to immobilize the synthesized Ni-Pd/core-shell nanoparticles onto a glassy carbon electrode (GCE). The modified electrode was characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS). Electrochemical data showed that the prepared biosensor had remarkably enhanced electrocatalytic activity toward glutamate. Moreover, superior reproducibility and excellent stability were observed (relative average deviation was 2.96% after continuous use of the same sensor for 60 times, and current responses remained at 94.85% of the initial value after 60 d). The sensor also demonstrated highly sensitive amperometric detection of glutamate with a low limit of detection (0.052 μM, S/N = 3), high sensitivity (4.768 μA μM(-1) cm(-2)), and a wide, useful linear range (0.1-500 μM). No interference from potential interfering species such as l-cysteine, ascorbic acid, and l-aspartate were noted. The determination of glutamate levels in actual samples achieved good recovery percentages.
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paper_title: Glutamate microbiosensors based on Prussian blue modified carbon fiber electrodes for neuroscience applications: in-vitro characterization

paper_content:

Herein we report a Prussian Blue modified carbon fiber electrode (CFE/PB) to be used in microbiosensors for glutamate monitoring in physiological applications as an alternative to the classical Pt and Pt-Ir transducers. Their low dimensions (∼250 μm CFE length and ∼10 μm diameter) are advantageous for measuring in living tissues. In addition, PB-modified microelectrodes allow the detection of enzyme-generated hydrogen peroxide at a low applied potential (∼0.0 V against SCE), contrasting the high potential used in many previous designs (∼0.7 V), decreasing the endogenous interference contributions. Moreover, the electrosynthesized polymer, poly-o-phenylenediamine (PoPD), was used to improve biosensor stability and selectivity. CFE/PB was conveniently characterized using impedance, Raman and XPS spectroscopies. Optimization of the fabrication procedure and analytical conditions is described, including activation of CFE/PB, enzyme enrichment, cross-linking, stabilization and anti-interference. A range of analytical parameters were also characterized such as sensitivity, limit of detection, linear range, and enzymatic loading. Finally, an optimized biosensor displaying a linear sensitivity of 135 ± 2 nA μM−1 cm−2 (n = 3), LOD of <2 μM, linear range up to 150 μM and effectively free of interference, is proposed as a suitable candidate for in-vivo glutamate monitoring in the central nervous system.
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paper_title: Construction of glutamate biosensor based on covalent immobilization of glutamate oxidase on polypyrrole nanoparticles/polyaniline modified gold electrode.

paper_content:

A method is described for construction of a highly sensitive electrochemical biosensor for detection of glutamate. The biosensor is based on covalent immobilization of glutamate oxidase (GluOx) onto polypyrrole nanoparticles and polyaniline composite film (PPyNPs/PANI) electrodeposited onto Au electrode. The enzyme electrode was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infra-red spectroscopy (FTIR) and electrochemical impedance spectroscopy (EIS). The biosensor showed optimum response within 3s at pH 7.5 (0.1 M sodium phosphate) and 35 °C, when operated at 50 mV s⁻¹. It exhibited excellent sensitivity (detection limit as 0.1 nM), fast response time and wider linear range (from 0.02 to 400 μM). Analytical recovery of added glutamate (5 mM and 10 mM) was 95.56 and 97%, while within batch and between batch coefficients of variation were 3.2% and 3.35% respectively. The enzyme electrode was used 100 times over a period of 60 days, when stored at 4 °C. The biosensor measured glutamate level in food stuff, which correlated well with a standard colorimetric method (r=0.99).
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paper_title: Electrochemically deposited iridium oxide reference electrode integrated with an electroenzymatic glutamate sensor on a multi-electrode array microprobe.

paper_content:

An implantable micromachined multi-electrode array (MEA) microprobe modified for utilization as a complete electrochemical biosensor for rapid glutamate detection is described. A post-fabrication method for electrochemical deposition of an iridium oxide (IrOx) film onto a designated microelectrode enabled incorporation of an IrOx reference electrode (RE) on the microprobe. The on-probe IrOx RE provides an alternative to the commonly utilized Ag/AgCl wire RE, which has been shown to be unstable and to cause an inflammatory response in living tissue. The IrOx film electrodeposited onto a platinum site was tested as part of a complete chemical sensing system that included a platinum counter electrode and enzymatic glutamate sensing electrodes all on a single silicon-based MEA platform. The thin film IrOx was mechanically robust enough to endure conditions of repeated heating and wetting during the MEA fabrication process. The pH dependence of the IrOx open circuit potential (OCP) was measured at -77±0.4 mV/pH and remained stable over a two-week period. The on-probe IrOx RE was tested in a two- and three-electrode system with glutamate biosensors. The biosensors were shown to detect a physiologically relevant range of glutamate concentrations and to reject the interferents, dopamine and ascorbic acid. By incorporating all of the electrodes onto a single device, baseline noise was reduced by an average of ∼61% in vitro and ∼71% in vivo with reduced tissue damage, since only a single probe needed to be implanted.
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paper_title: Low potential detection of glutamate based on the electrocatalytic oxidation of NADH at thionine/single-walled carbon nanotubes composite modified electrode

paper_content:

A glutamate biosensor based on the electrocatalytic oxidation of reduced nicotinamide adenine dinucleotide (NADH), which was generated by the enzymatic reaction, was developed via employing a single-walled carbon nanotubes/thionine (Th-SWNTs) nanocomposite as a mediator and an enzyme immobilization matrix. The biosensor, which was fabricated by immobilizing glutamate dehydrogenase (GlDH) on the surface of Th-SWNTs, exhibited a rapid response (ca. 5s), a low detection limit (0.1 microM), a wide and useful linear range (0.5-400 microM), high sensitivity (137.3+/-15.7) microA mM(-1)cm(-2), higher biological affinity, as well as good stability and repeatability. In addition, the common interfering species, such as ascorbic acid, uric acid, and 4-acetamidophenol, did not cause any interference due to the use of a low operating potential (190 mV vs. NHE). The biosensor can be used to quantify the concentration of glutamate in the physiological level. The Th-SWNTs system represents a simple and effective approach to the integration of dehydrogenase and electrodes, which can provide analytical access to a large group of enzymes for wide range of bioelectrochemical applications including biosensors and biofuel cells.
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paper_title: A microelectrode biosensor for real time monitoring of L-glutamate release.

paper_content:

We have developed an amperometric microbiosensor for real time monitoring L-glutamate release in neural tissue, based on enzymatic oxidation catalyzed by the L-glutamate oxidase. By means of a sol-gel coating method, L-glutamate oxidase was entrapped in a biocompatible gel layer that provided a benign environment and retained enzyme activity on the surface of Pt microelectrode. Prior to gel layer formation, a modification on the surface of Pt microelectrode with poly(phenylene diamine) enabled the microbiosensor screen majority of common potential interfering substances existing in physiological samples. The miniaturized biosensor achieved a steady state response to l-glutamate within 10 s and exhibited a linear dependence on the concentration of L-glutamate from 0.5 to 100 micromol L(-1) with a high sensitivity of 279.4 +/- 2.0 microA (mmol L(-1))(-1) cm(-2) (n = 4, R.S.D. = 2.8%). The microbiosensor also exhibited excellent long-term stability in dry storage. We have successfully used the microbiosensor for real time measuring of L-glutamate in vivo.
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paper_title: l- Glutamate biosensor based on l-glutamate oxidase immobilized onto ZnO nanorods/polypyrrole modified pencil graphite electrode

paper_content:

Abstract A method is described for the construction of a highly sensitive electrochemical biosensor for the detection of l -glutamate. Such a biosensor is based on immobilization of glutamate oxidase (GluO x ) onto zinc oxide nanorods (ZnONRs)/polypyrrole (PPy) composite. This composite was electro-deposited onto a pencil graphite (PG) electrode. The enzyme electrode was characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), Fourier transform infra-red spectroscopy (FTIR) and cyclic voltammetry (CV). The biosensor showed optimum response at pH 8.5 (0.1 M Tris–HCl buffer) and 30 °C, when operated at 20 mV s −1 . The biosensor exhibited excellent sensitivity (detection limit as 0.18 nM), fast response time (less than 5 s) and wide linear range (0.02–500 μM). Analytical recovery of added l -glutamate (20 and 40 μM) in commercial Chinese soup were 95.40 and 97.56% respectively .The within batch and between batch coefficients of variation (CV) in measurement of l -glutamate in commercial Chinese soup were 2.35% and 4.5% respectively. The enzyme electrode lost 30% of its initial activity after 100 uses over a period of 90 days, when stored at 4 °C.
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paper_title: Development of a novel reagentless, screen-printed amperometric biosensor based on glutamate dehydrogenase and NAD+, integrated with multi-walled carbon nanotubes for the determination of glutamate in food and clinical applications

paper_content:

A screen printed carbon electrode (SPCE) containing the electrocatalyst Meldola's Blue (MB) has been investigated as the base transducer for a reagentless glutamate biosensor. The biopolymer chitosan (CHIT) and multiwalled carbon nanotubes (MWCNTs) were used to encapsulate the enzyme glutamate dehydrogenase (GLDH) and the co-factor nicotinamide adenine dinucleotide (NAD+). The biosensor was fabricated by sequentially depositing the components on the surface of the transducer (MB-SPCE) in a layer-by-layer process, details of which are included in the paper. Each layer was optimised to construct the reagentless device. The biosensor was used in conjunction with amperometry in stirred solution using an applied potential of +0.1 V (vs. Ag/AgCl). Optimum conditions for the analysis of glutamate were found to be: temperature, 35 °C; phosphate buffer, pH 7 (0.75 mM, containing 0.05 M NaCl). The linear range of the reagentless biosensor was found to be 7.5–105 μM, and limit of detection was found to be 3 μM (based on n = 5, CV: 8.5% based on three times signal to noise) and the sensitivity was 0.39 nA/μM (±0.025, coefficient of variation (CV) of 6.37%, n = 5). The response time of the biosensor was 20–30 s. A food sample was analysed for monosodium glutamate (MSG). The endogenous content of MSG was 90.56 mg/g with a CV of 7.52%. The reagentless biosensor was also used to measure glutamate in serum. The endogenous concentration of glutamate was found to be 1.44 mM (n = 5), CV: 8.54%. The recovery of glutamate in fortified serum was 104% (n = 5), CV of 2.91%.
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paper_title: Highly sensitive and selective glutamate microbiosensor based on cast polyurethane/AC-electrophoresis deposited multiwalled carbon nanotubes and then glutamate oxidase/electrosynthesized polypyrrole/Pt electrode

paper_content:

Abstract A highly sensitive and selective glutamate microbiosensor based on polypyrrole (PPy), multiwalled carbon nanotubes (MWCNT) and glutamate oxidase (GluOx) deposited on the transducer platinum electrode (Pt) is described. The sensor consists of a permselective membrane of polypyrrole for the rejection of interferences, followed by a layer of multiwalled carbon nanotubes and glutamate oxidase deposited by asymmetrical alternating current electrophoretic deposition (AC-EPD). The biosensor has a high sensitivity (3.84 nA/(μM mm 2 )), low response to interferences such as ascorbic acid, uric acid and acetaminophen, a fast response time (7 s), low detection limit (∼0.3 μM), a linear range of 140 μM and a satisfactory stability. In order to improve the linear range and the stability, a thin layer of polyurethane (PU) was applied to the Pt/PPy/MWCNT/GluOx sensor. The resulting sensor with the PU outer membrane showed an increase in the linear range up to ∼500 μM glutamate and has a better stability at the expense of a decrease in sensitivity (2.5 nA/(μM mm 2 )) and an increase in the response time (15 s).
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paper_title: An amperometric glutamate biosensor based on immobilization of glutamate oxidase onto carboxylated multiwalled carbon nanotubes/gold nanoparticles/chitosan composite film modified Au electrode.

paper_content:

A method is described for the construction of a novel amperometric glutamate biosensor based on covalent immobilization of glutamate oxidase (GluOx) onto, carboxylated multi walled carbon nanotubes (cMWCNT), gold nanoparticles (AuNPs) and chitosan (CHIT) composite film electrodeposited on the surface of a Au electrode. The GluOx/cMWCNT/AuNP/CHIT modified Au electrode was characterized by scanning electron microscopy (SEM), fourier transform infra-red (FTIR) spectroscopy, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The biosensor measured current due to electrons generated at 0.135V against Ag/AgCl from H2O2, which is produced from glutamate by immobilized GluOx. The biosensor showed optimum response within 2s at pH 7.5 and 35°C. A linear relationship was obtained between a wide glutamate concentration range (5-500μM) and current (μA) under optimum conditions. The biosensor showed high sensitivity (155nA/μM/cm(2)), low detection limit (1.6μM) and good storage stability. The biosensor was unaffected by a number of serum substances at their physiological concentrations. The biosensor was evaluated and employed for determination of glutamate in sera from apparently healthy subjects and persons suffering from epilepsy.
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paper_title: Glutamate oxidase biosensor based on mixed ceria and titania nanoparticles for the detection of glutamate in hypoxic environments.

paper_content:

We report on the design and development of a glutamate oxidase (GmOx) microelectrode for measuring l-glutamic acid (GluA) in oxygen-depleted conditions, which is based on the oxygen storage and release capacity of cerium oxides. To fabricate the biosensor, a nanocomposite of oxygen-rich ceria and titania nanoparticles dispersed within a semi-permeable chitosan membrane was co-immobilized with the enzyme GmOx on the surface of a Pt microelectrode. The oxygen delivery capacity of the ceria nanoparticles embedded in a biocompatible chitosan matrix facilitated enzyme stabilization and operation in oxygen free conditions. GluA was measured by amperometry at a working potential of 0.6 V vs Ag/AgCl. Detection limits of 0.594 µM and 0.493 µM and a sensitivity of 793 pA/µM (RSD 3.49%, n=5) and 395 pA/µM (RSD 2.48%, n=5) were recorded in oxygenated and deoxygenated conditions, with response times of 2s and 5s, respectively. The biosensor had good operational stability and selectivity against common interfering substances. Operation of the biosensor was tested in cerebrospinal fluid. Preliminary in vivo recording in Sprague-Dawley rats to monitor GluA in the cortex during cerebral ischemia and reperfusion demonstrate a potential application of the biosensor in hypoxic conditions. This method provides a solution to ensure functionality of oxidoreductase enzymes in oxygen-free environments.
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paper_title: Invariant mantling of growth cones by Schwann cell precursors characterize growing peripheral nerve fronts

paper_content:

Little is known about the cytoarchitecture of growth fronts in developing mammalian nerves. We report here the first quantitative, ultrastructural analysis of growth cones (GCs) and their immediate cellular and tissue environment at tips of growing nerves that are nearing their targets in fore limbs of E14 rat embryos. Schwann cell precursor (SCP) marker, p75 neurotrophin receptor, and growth cone marker, SCG10, were used to identify nerve fronts, respectively. Using confocal 3D reconstructions and immunoelectron microscopy, we found that growth cone and Schwann cell precursor migrate together at the nerve front, where growth cone contact adjacent growth cone and Schwann cell precursor with similar frequency. Schwann cell precursor are extensively connected by adherens junctions and form elaborate scaffolds that enmantle growth cone at nerve fronts, so that 80% of the nerve front surface is covered by Schwann cell precursor. Although they interdigitate in complex ways among growth cone, the total contact area between growth cone and glial membranes is remarkably constant among the 100 growth fronts analyzed. In contrast to this consistency, other growth cone contacts varied markedly from front to front such that the frequencies of GC-GC contacts are increasing proportional to their decreasing contacts with mesenchymal tissue. Thus, at the nerve front, it is the Schwann cell precursor that are most exposed to extracellular environment while forming a surprisingly invariant substrate for advancing growth cone. This study shows for the first time that Schwann cell precursor are close and consistent cellular companions of growth cone in their approach to their final targets in the developing limb and suggests a previously unappreciated role for Schwann cell precursor in growth cone advance through the limb mesenchyme.
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paper_title: Disruptions in the Regulation of Extracellular Glutamate by Neurons and Glia in the Rat Striatum Two Days after Diffuse Brain Injury

paper_content:

Abstract Disrupted regulation of extracellular glutamate in the central nervous system contributes to and can exacerbate the acute pathophysiology of traumatic brain injury (TBI). Previously, we reported increased extracellular glutamate in the striatum of anesthetized rats 2 days after diffuse brain injury. To determine the mechanism(s) responsible for increased extracellular glutamate, we used enzyme-based microelectrode arrays (MEAs) coupled with specific pharmacological agents targeted at in vivo neuronal and glial regulation of extracellular glutamate. After TBI, extracellular glutamate was significantly increased in the striatum by (∼90%) averaging 4.1±0.6 μM compared with sham 2.2±0.4 μM. Calcium-dependent neuronal glutamate release, investigated by local application of an N-type calcium channel blocker, was no longer a significant source of extracellular glutamate after TBI, compared with sham. In brain-injured animals, inhibition of glutamate uptake with local application of an excitatory amino a...
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paper_title: Disposable sensor based on enzyme-free Ni nanowire array electrode to detect glutamate.

paper_content:

Enzyme free electrochemical sensor platform based on a vertically aligned nickel nanowire array (NiNAE) and Pt coated nickel nanowire array (Pt/NiNAE) have been developed to detect glutamate. Morphological characterisation of Ni electrodes was carried out using scanning and transmission electron microscopy combined with energy dispersive X-ray (SEM-EDX), X-ray diffraction (XRD) and transmission electron microscopy (TEM). Cyclic voltammetry (CV) and amperometry were used to evaluate the catalytic activity of the NiNAE and the Pt/NiNAE for glutamate. It has been found that both NiNAE and Pt/NiNAE electrodes showed remarkably enhanced electrocatalytic activity towards glutamate compared to planar Ni electrodes, and showed higher catalytic activity when compared to other metallic nanostructure electrodes such as gold nanowire array electrodes (AuNAE) and Pt coated gold nanowire array electrode (Pt/AuNAE). The sensitivity of NiNAE and Pt/NiNAE has been found to be 65 and 96 μA mM(-1) cm(-2), respectively, which is approximately 6 to 9 times higher than the state of the art glutamate sensor. Under optimal detection conditions, the as prepared sensors exhibited linear behaviour for glutamate detection in the concentration up to 8mM for both NiNAE and Pt/NiNAE with a limit of detection of 68 and 83 μM, respectively. Experimental results show that the vertically aligned ordered nickel nanowire array electrode (NiNAE) has significant promise for fabricating cost effective, enzyme-less, sensitive, stable and selective sensor platform.
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paper_title: Beyond the role of glutamate as a neurotransmitter

paper_content:

Glutamate is the principal excitatory neurotransmitter of the central nervous system, but many studies have expanded its functional repertoire by showing that glutamate receptors are present in a variety of non-excitable cells. How does glutamate receptor activation modulate their activity? Do non-excitable cells release glutamate, and, if so, how? These questions remain enigmatic. Here, we review the current knowledge on glutamatergic signalling in non-neuronal cells, with a special emphasis on astrocytes.
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paper_title: Glutamate as a Neurotransmitter in the Brain: Review of Physiology and Pathology

paper_content:

Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), a-amino-3-hydroxy-5-methyl-4-isox-azolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.
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paper_title: Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus

paper_content:

This study examined whether xanthohumol, a hop-derived prenylated flavonoid present in beer, affects glutamate release in the rat hippocampus. In the rat hippocampal nerve terminals (synaptosomes), xanthohumol inhibited the release of 4-aminopyridine (4-AP)-evoked glutamate and the elevation of cytosolic Ca2+ concentration, whereas it had no effect on 4-AP-mediated depolarization. The inhibitory effect of xanthohumol on the evoked glutamate release was prevented by removing extracellular Ca2+, using the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-CgTX MVIIC, the calmodulin antagonists W7 and calmidazolium, and the protein kinase A inhibitor H89; however, no such effect was observed when the G-protein inhibitor N-ethylmaleimide was used. In addition, immunocytochemical data demonstrated that GABAA receptors are present in the hippocampal synaptosomes and that the xanthohumol effect on evoked glutamate release was antagonized by the GABAA receptor antagonist SR95531. Furthermore, in slice preparations, xanthohumol reduced the frequency of miniature excitatory postsynaptic currents without affecting their amplitude. We conclude that xanthohumol acts at GABAA receptors present in the hippocampal nerve terminals to decrease the Ca2+ influx through N- and P/Q-type Ca2+ channels, which subsequently suppresses the Ca2+-calmodulin/PKA cascade to decrease the evoked glutamate release.
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paper_title: Mitochondrial dysfunction and loss of glutamate uptake in primary astrocytes exposed to titanium dioxide nanoparticles

paper_content:

Titanium dioxide (TiO2) nanoparticles are currently the second most produced engineered nanomaterial in the world with vast usage in consumer products leading to recurrent human exposure. Animal studies indicate significant nanoparticle accumulation in the brain while cellular toxicity studies demonstrate negative effects on neuronal cell viability and function. However, the toxicological effects of nanoparticles on astrocytes, the most abundant cells in the brain, have not been extensively investigated. Therefore, we determined the sub-toxic effect of three different TiO2 nanoparticles (rutile, anatase and commercially available P25 TiO2 nanoparticles) on primary rat cortical astrocytes. We evaluated some events related to astrocyte functions and mitochondrial dysregulation: (1) glutamate uptake; (2) redox signaling mechanisms by measuring ROS production; (3) the expression patterns of dynamin-related proteins (DRPs) and mitofusins 1 and 2, whose expression is central to mitochondrial dynamics; and (4) mitochondrial morphology by MitoTracker® Red CMXRos staining. Anatase, rutile and P25 were found to have LC50 values of 88.22 ± 10.56 ppm, 136.0 ± 31.73 ppm and 62.37 ± 9.06 ppm respectively indicating nanoparticle specific toxicity. All three TiO2 nanoparticles induced a significant loss in glutamate uptake indicative of a loss in vital astrocyte function. TiO2 nanoparticles also induced an increase in reactive oxygen species generation, and a decrease in mitochondrial membrane potential, suggesting mitochondrial damage. TiO2 nanoparticle exposure altered expression patterns of DRPs at low concentrations (25 ppm) and apoptotic fission at high concentrations (100 ppm). TiO2 nanoparticle exposure also resulted in changes to mitochondrial morphology confirmed by mitochondrial staining. Collectively, our data provide compelling evidence that TiO2 nanoparticle exposure has potential implications in astrocyte-mediated neurological dysfunction.
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paper_title: Hierarchical and hybrid RGO/ZIF-8 nanocomposite as electrochemical sensor for ultrasensitive determination of dopamine

paper_content:

Abstract A hierarchical and hybrid nanocomposite of reduced graphene oxide/zeolitic imidazolate framework-8 (RGO/ZIF-8) has been successfully fabricated by the RGO as template for the in situ growth of ZIF-8. The morphology and structure of the resulted RGO/ZIF-8 nanocomposite were characterized by using scanning electron microscopy (SEM) and X-ray diffraction (XRD). It was demonstrated that ZIF-8 nanoparticles anchored and grew well on the surfaces of RGO. The electrocatalytic activity of the RGO/ZIF-8 towards the dopamine (DA) was investigated using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results demonstrated the fabricated RGO/ZIF-8 sensor exhibited high sensitivity for the determination of DA, owing to the synergistic effect from highly electrical conductivity of RGO and porosity of ZIF-8. Under the optimal conditions, the linear response range for DA was from 1.0 × 10 − 7 to 1.0 × 10 − 4 mol L − 1 and the detection limit of DA was estimated to be as low as 3 × 10 − 8 mol L − 1 . Moreover, the prepared electrochemical sensor also showed excellent selectivity for DA detection in the presence of ascorbic acid (AA) and prospective results in real samples detection.
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paper_title: Detection of Dopamine by a Biomimetic Electrochemical Sensor Based on Polythioaniline-Bridged Gold Nanoparticles.

paper_content:

A new biomimetic electrochemical sensor was developed for the detection of dopamine based on a glassy carbon electrode modified with electrochemically generated gold nanoparticles. The preparation of the polymer is simple and cost-effective, achieving the polymerization of thioaniline and generation of gold nanoparticles in a single step by cyclic voltammetry, in the presence of the target molecule, dopamine. After extraction, the imprinted polymer exhibits high sensitivity and selectivity for dopamine. Moreover, the developed imprinted polymer film allows the fast, direct detection of dopamine without the need of a redox mediator. The formation of a self-assembled monolayer of the monomer prior to electropolymerization ensures the adherence of the film onto the electrode surface, conferring good stability to the sensor (over two weeks). Cyclic voltammetry, electrochemical impedance spectroscopy, atomic force microscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy were used for the complete characterization of the developed sensor, and differential pulse voltammetry was used for its testing.
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paper_title: Electrochemically deposited iridium oxide reference electrode integrated with an electroenzymatic glutamate sensor on a multi-electrode array microprobe.

paper_content:

An implantable micromachined multi-electrode array (MEA) microprobe modified for utilization as a complete electrochemical biosensor for rapid glutamate detection is described. A post-fabrication method for electrochemical deposition of an iridium oxide (IrOx) film onto a designated microelectrode enabled incorporation of an IrOx reference electrode (RE) on the microprobe. The on-probe IrOx RE provides an alternative to the commonly utilized Ag/AgCl wire RE, which has been shown to be unstable and to cause an inflammatory response in living tissue. The IrOx film electrodeposited onto a platinum site was tested as part of a complete chemical sensing system that included a platinum counter electrode and enzymatic glutamate sensing electrodes all on a single silicon-based MEA platform. The thin film IrOx was mechanically robust enough to endure conditions of repeated heating and wetting during the MEA fabrication process. The pH dependence of the IrOx open circuit potential (OCP) was measured at -77±0.4 mV/pH and remained stable over a two-week period. The on-probe IrOx RE was tested in a two- and three-electrode system with glutamate biosensors. The biosensors were shown to detect a physiologically relevant range of glutamate concentrations and to reject the interferents, dopamine and ascorbic acid. By incorporating all of the electrodes onto a single device, baseline noise was reduced by an average of ∼61% in vitro and ∼71% in vivo with reduced tissue damage, since only a single probe needed to be implanted.
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paper_title: Water based homogenous carbon ink modified electrode as an efficient sensor system for simultaneous detection of ascorbic acid, dopamine and uric acid

paper_content:

Abstract Development of new sensor material suitable for simple, cost effective and quick practical application is a demanding research interest in electroanalytical chemistry. Carbon based inks prepared using different type carbon materials and binders as a gel or suspension have been often used as active sensor materials. Unfortunately, those systems are involved with complicated preparation route and usage of hazardous chemicals. Herein, we report a water based carbon ink composed of low cost carbon black powder, chitosan and acetic acid (prepared within 15 ± 2 min) for electrochemical sensor applications. A new carbon ink modified electrode was fabricated in this work by drop-casting of micro-litre quantity of the CB-Chit ink on a cleaned glassy carbon electrode (GCE) followed by air drying in room temperature for 10 ± 2 min. The CB-Chit ink modified GCE (GCE/CB-Chit) showed enhanced electrical conductivity, surface area and electrochemical activity than that of the unmodified GCE. Investigated simultaneous electrochemical oxidation and sensing of three biologically important molecules such as ascorbic acid, dopamine and uric acid on GCE/CB-Chit displayed excellent peak current signals at well-defined peak potentials with linear concentration ranges of 25–1600, 0.1–1400, and 5–1800 μM and detection limit of 0.1 μM (S/N = 3) for the all analytes. The newly fabricated sensor was validated by applying to the detection of AA, DA, and UA in vitamin C tablets, dopamine hydrochloride injection and human urine real samples. The sensor can be operated without any surface pre-treatment and analyte adsorption, unlike to the carbon nanotube and graphite based electrode systems with serious adsorption complications.
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paper_title: L-cysteine capped ZnS:Mn quantum dots for room-temperature detection of dopamine with high sensitivity and selectivity

paper_content:

Dopamine (DA) is one of the most important catecholamine neurotransmitters of the human central nervous system, and is involved in many behavioral responses and brain functions. Below normal DA levels in biological fluids can lead to different neurodegenerative conditions. For excess DA levels, a failure in energy metabolism is indicated. In this study, a facile room-temperature phosphorescence sensor is developed to detect DA based on l-cysteine capped Mn doped ZnS quantum dots (l-cys ZnS:Mn QDs). The QDs display a prominent orange emission band peaking at ~598nm, which is strongly quenched upon addition of DA in alkaline medium. The sensor exhibits a linear working range of ~0.15-3.00μM, and a limit of detection of ~7.80nM. These results are explained in terms of a pH-dependent electron transfer process, in which the oxidized dopamine quinone functions as an efficient electron acceptor. The QDs-based sensor shows a high selectivity to DA over common interfering biomolecules (including some amino acids, ascorbic acid, chloride and glucose). The sensor has been successfully applied for the detection of DA in urine samples, yielding recoveries as high as 93%. Our findings indicate that our developed sensor exhibits high sensitivity and reproducibility to determine DA even in biological fluids where DA is at low levels, e.g., in the central nervous system, which is the usual clinical profile of a neurodegenerative disorder associated to the Parkinson's disease.
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paper_title: A facile preparation of Au—SiO2 nanocomposite for simultaneous electrochemical detection of dopamine and uric acid

paper_content:

Abstract We report an electrochemical biosensor based on Au—SiO2 nanocomposite for the detection of dopamine and uric acid. The nanocomposite was prepared by a simple wet chemical process and the characterisation was carried out using transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Cyclic voltammetry (CV) was used to assess the electrocatalytic response of Au-SiO2/GCE towards dopamine and uric acid. Compared to Au/GCE and SiO2/GCE, the Au-SiO2/GCE exhibited high electrocatalytic response which is attributed to the increased surface area and conductivity of the nanocomposite. The detection of dopamine and uric acid was performed by using differential pulse voltammetry (DPV) which displayed two linear ranges from 10 μM-100 μM and 200 μM-500 μM with a detection limit of 1.98 μM for dopamine and a linear range from 10 μM-500 μM with a detection limit of 2.58 μM for uric acid. The simultaneous detection of dopamine and uric acid was carried out which showed a peak to peak separation of 215 mV. The sensor showed excellent sensitivity for dopamine and uric acid with good stability and reproducibility. Further, the detection of dopamine and uric acid in serum sample analysis was performed successfully with satisfactory recovery values.
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paper_title: Fabrication of 3D honeycomb-like porous polyurethane-functionalized reduced graphene oxide for detection of dopamine.

paper_content:

Abstract A three dimensional reduced graphene oxide/polyurethane (RGO-PU) porous material with connected pores was prepared by physical adsorption of RGO onto the surface of porous PU. The porous PU was prepared by directional melt crystallization of a solvent, which produced high pores with controlled orientation. The prepared RGO-PU was characterized by scanning electron microscopy, spectroscopy and electro-chemical methods. The RGO-PU porous material revealed better electrochemical performance, which might be attributed to the robust structure, superior conductivity, large surface area, and good flexibility. Differential pulse voltammetry (DPV) analysis of DA using the RGO-PU exhibited a linear response range over a wide DA concentration of 100–1150 pM, with the detection limit of 1 pM. This sensor exhibited outstanding anti-interference ability towards co-existing molecules with good stability, sensitivity, and reproducibility. Furthermore, the fabricated sensor was successfully applied for the quantitative analysis of DA in human serum and urine samples with acceptable recovery, which indicates its feasibility for practical application.
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paper_title: Facile synthesis of nitrogen-doped graphene aerogels for electrochemical detection of dopamine

paper_content:

Abstract Nitrogen-doped graphene aerogels with three-dimensional network structures are fabricated using hydrothermal method which includes the reduction of graphene oxide by organic amine and self-assembly of reduced graphene oxide. The effect of amine-containing compounds including aniline, 2-aminoethanol, ethylenediamine, melamine and chitosan on the assembly of nitrogen-doped graphene aerogel is investigated. The microstructure and chemical composition of nitrogen-doped graphene aerogels are characterized. The results reveal that nitrogen-doped graphene aerogel prepared using aniline as nitrogen source possesses a large specific surface area, high nitrogen content, good mechanical strength and excellent electrical conductivity. Based on these features, the as-prepared nitrogen-doped graphene aerogel shows high performance in electrochemical detection of dopamine in the presence of uric acid and ascorbic acid. Given the facile and scalable processability of aerogels, the proposed nitrogen-doped graphene aerogels are expected to have potential applications in sensors and other related devices.
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paper_title: An electrochemical sensor for selective detection of dopamine based on nickel tetrasulfonated phthalocyanine functionalized nitrogen-doped graphene nanocomposites

paper_content:

Abstract A novel electrochemical sensing platform based on nitrogen-doped graphene (N-G)/nickel tetrasulfonated phthalocyanine (NiTsPc) nanocomposites has been developed for selective determination of dopamine (DA). NiTsPc was immobilized on N-G matrix via π-π interaction, while N-G provided a compatible microenvironment for NiTsPc to enhance electron transfer and to retain its electrocatalytic activity as well. The N-G/NiTsPc nanocomposite was characterized by using transmission electron microscopy (TEM), electrochemical impedance spectroscopy (EIS), X-ray photoelectron spectroscopy (XPS) and cyclic voltammetry (CV). The proposed modified electrode presented superior catalytic efficiency for DA in the presence of ascorbic acid (AA) and uric acid (UA) owing to the synergistic effect of N-G and NiTsPc. The sensors also exhibited a wide linear range from 1 × 10 − 7 to 2 × 10 − 4 M and a limit of detection as low as 100 nM with high sensitivity of 88.9 μA mM − 1 .
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paper_title: Facile fabrication of hierarchical nanoporous AuAg alloy and its highly sensitive detection towards dopamine and uric acid

paper_content:

Abstract Hierarchical nanoporous AuAg (HNP-AuAg) alloy with bimodal ligament/pore size distributions is fabricated by means of selective dealloying of Al and redealloying of Ag from AuAgAl source alloy combined with annealing operation. The as-made HNP-AuAg alloy consists of interconnected hierarchical nanoporous architecture with two order ligament/pore size distributions around 100 and 10 nm in all three dimensions. Characterized by such the specific nanoporous architecture, HNP-AuAg alloy exhibits excellent electrocatalytic activities towards the simultaneous and individual oxidation of dopamine (DA) and uric acid (UA) in the absence and presence of ascorbic acid. The electrochemical sensing towards DA and UA on HNP-AuAg alloy displays fast response and low detection limit of 0.2 μM and 1.0 μM in a wide linear range of 5–335 μM and 5–425 μM, respectively. More importantly, the as-made HNP-AuAg alloy behaves long-term stability and reproducibility towards the detection of DA and UA. Along with these attractive features, HNP-AuAg shows great application potential for constructing electrochemical sensors to the detection of DA and UA.
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paper_title: Catalytic activity of biomimetic model of cytochrome P450 in oxidation of dopamine.

paper_content:

The introduction of electron-withdrawing group into porphyrin molecule as cytochrome P450 model can tune the energy level and have an effect on the electronic structure. In this work, linking with the strong electron-withdrawing fluorine atoms, a starburst dendritic molecule, 5,10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphyrin iron (III) chloride (FeTFPP), containing a saddle-shaped porphyrin as the central core and four pentafluorophenyl rings as the peripheral functional groups was successfully synthesized. Subsequently, the macrocyclic conjugate polymer film of FeTFPP was achieved via a low-cost electrochemical method and exploited as an efficient mimetic enzyme. Furthermore, a biomimetic sensor was constructed by the poly(FeTFPP) film and graphene (rGO) sheet (rGO-poly(FeTFPP)) for selective and sensitive detection of dopamine (DA). Here, the FeTFPP polymer performs three functions: electrochemical recognition (owing to the hydrogen bonding between the strongly electronegative fluorine atoms and DA), biomimetic microenvironment (owing to interaction between porphyrin core and DA), electrocatalysis (owing to remarkable catalytic ability of iron (III) ion). Under optimum conditions, the response to DA was linear in the concentration range between 0.05 to 300μM, and the detection limit was 0.023μM. In addition, we applied the rGO-poly(FeTFPP) film to detect DA in real samples and the results implied its feasibility for practical application. As a result, it is believed that the rGO-poly(FeTFPP) film is one of the promising biomimetic catalysts for electrocatalysis and relevant fields.
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paper_title: Physiological Level and Selective Electrochemical Sensing of Dopamine by a Solution Processable Graphene and its Enhanced sensing property in general

paper_content:

Abstract Here in, for the first time, mechanically pulverized graphite (pGr) has been used as an electrode material for the electrochemical (EC) sensing of analytes such as dopamine (DA) and ascorbic acid (AA). The pGr modified electrode exhibits a wide linear response range over the physiological concentration range of DA and AA, and the lowest limiting value of detection (LOD) so far reported for DA and AA of 1 nM, subjected to S/N = 3. The PGr demonstrates selectivity towards DA in the presence of AA and is able to simultaneously detect DA, AA and uric acid (UA). The enhanced and selective sensing of pGr towards DA is assigned to its intact aromatic basal plane structure which promotes the preferential adsorption of DA due to the similarities in their structures. The dispersibility of pGr in water and the formation of Gr nanosheets are explained by the hydrophilic edges. The sensing performance of pGr towards DA and AA is found to be superior to that of reduced graphene oxide (rGO) and graphene oxide (GO). Our results demonstrate the feasibility and the merits of pGr in the EC sensing applications and give insight to its structure.
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paper_title: An electrochemical ratiometric sensor based on 2D MOF nanosheet/Au/polyxanthurenic acid composite for detection of dopamine

paper_content:

Abstract In this study, a novel Cu-based metal−organic frameworks (Cu-MOFs) composite material was prepared, and used to develop a sensitive and efficient electrochemical ratiometric sensor for dopamine detection. Gold nanoparticles (NPs) and the conductive poly(xanthurenic acid) p(XA) were assembled on the Cu-tetrakis (4-carboxyphenyl) porphyrin (TCPP) surface by electrodeposition and cyclic voltammetry (CV) method, which greatly improved the electrocatalytic performance of the Cu-MOF modified electrode. Two substances (dopamine/DA, paracetamol/PA) with different electrochemical peaks were added to the electrolyte solutions, where DA was the analyte and PA was as a reference. The ratiometric value of differential pulse voltammetry (DPV) oxidation current (IDA/IPA) linearly increased with the increasing concentration of DA with low detection limit. This electrochemical ratiometric approach based on the metal−organic framework composites is expected to be a valuable strategy for detection of other analytes.
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paper_title: An electrochemical biosensor for sensitive detection of nicotine-induced dopamine secreted by PC12 cells

paper_content:

Abstract A facile, sensitive and selective electrochemical biosensor for the detection of dopamine (DA) released from nicotine-stimulated PC12 cells was fabricated by using a poly-celestine blue (CB) modified glassy carbon electrode (GCE). The poly-CB film was prepared by controlled electropolymerization and has about 5 nm thick on the GCE surface. In the optimal experimental condition, the poly-CB modified GCE showed excellent electrocatalytic activity toward the oxidation of DA. The response signal obtained by differential pulse voltammetry displayed a good linear relationship between the current response signal and the DA concentrations in range from 10 nmol L−1 to 0.7 μmol L−1 and 1 μmol L−1 to 10 μmol L−1 with a detection limit of 1.2 nmol L−1 (S/N = 3) and sensitivity of 17.0134 μA cm2 μM−1. In addition, the poly-CB modified GCE has successfully been applied to determine nicotine-induced dopamine released from PC12 cells with satisfactory recovery. The developed method held great potential for the detection of dopamine in biological samples and would bring great convenience to the diagnosis of diseases associated with deficiency in dopamine.
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paper_title: Dopamine biosensor based on surface functionalized nanostructured nickel oxide platform.

paper_content:

A dopamine biosensor has been developed using nickel oxide nanoparticles (NPs) and tyrosinase enzyme conjugate. Nickel oxide (NiO) NPs were synthesized by sol-gel method using anionic surfactant, sodium dodecyl sulphate (SDS), as template to control the size of synthesized nanoparticles. The structural and morphological studies of the prepared NPs were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. Afterwards, tyrosinase enzyme molecules were adsorbed on NiO NPs surface and enzyme coated NPs were deposited on indium tin oxide (ITO) coated flexible polyethylene terephthalate (PET) substrate by solution casting method. The formation of enzyme-NPs conjugate was investigated by atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR) techniques and used in selective detection and estimation of neurochemical dopamine by electrochemical method. The fabricated Tyrosinase/NiO/ITO electrode exhibits high sensitivity of 60.2nA/µM in linear detection range (2-100μM) with a detection limit of 1.038μM. The proposed sensor had a response time of 45s, long shelf life (45 days) with good reproducibility and selectivity in presence of interfering substances and was validated with real samples. The tyrosinase enzyme functionalized NiO platform has good bio-sensing efficacy and can be used in detection of other catecholamines and phenolic neurochemicals.
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paper_title: Morphology-controlled synthesis of Bi 2 S 3 nanorods-reduced graphene oxide composites with high-performance for electrochemical detection of dopamine

paper_content:

Abstract Bi 2 S 3 nanorods anchored over reduced graphene oxide (rGO/Bi 2 S 3 ) were successfully synthesized via a one-pot hydrothermal process, where in-situ generation of Bi 2 S 3 nanorods and reduction of GO occurred simultaneously. Moreover, the controlled synthesis of rGO/Bi 2 S 3 nanocomposite with tunable size was achieved by adjusting the dosage of GO. The nanocomposites were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectrometry (EDX), X-ray diffraction (XRD), Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy, respectively. Because of the particular construction of as-prepared nanocomposite and the synergistic effect between rGO sheets and Bi 2 S 3 nanorods, the rGO/Bi 2 S 3 film can effectively accelerate electron transport and extend catalytic active sites, leading to the remarkable electrochemical performance for dopamine sensing. The rGO/Bi 2 S 3 -1/GCE sensor exhibited excellent electrocatalytic activity toward the dopamine oxidation with a wide linear range of 0.01–40 μM and a low detection limit of 12.3 nM. Furthermore, the as-prepared sensor could be feasibly applied to detect dopamine in urine samples. Hence, the prepared rGO/Bi 2 S 3 composite is one of the low cost, extremely promising and nontoxicity materials for electrocatalysis and relevant fields.
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paper_title: Simultaneous voltammetric determination of dopamine and epinephrine in human body fluid samples using a glassy carbon electrode modified with nickel oxide nanoparticles and carbon nanotubes within a dihexadecylphosphate film

paper_content:

A simple and highly selective electrochemical method was developed for the single or simultaneous determination of dopamine (DA) and epinephrine (EP) in human body fluids using a glassy carbon electrode modified with nickel oxide nanoparticles and carbon nanotubes within a dihexadecylphosphate film using square-wave voltammetry (SWV) or differential-pulse voltammetry (DPV). Using DPV with the proposed electrode, a separation of ca. 360 mV between the peak reduction potentials of DA and EP present in binary mixtures was obtained. The analytical curves for the simultaneous determination of dopamine and epinephrine showed an excellent linear response, ranging from 7.0 × 10(-8) to 4.8 × 10(-6) and 3.0 × 10(-7) to 9.5 × 10(-6) mol L(-1) for DA and EP, respectively. The detection limits for the simultaneous determination of DA and EP were 5.0 × 10(-8) mol L(-1) and 8.2 × 10(-8) mol L(-1), respectively. The proposed method was successfully applied in the simultaneous determination of these analytes in human body fluid samples of cerebrospinal fluid, human serum and lung fluid.
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paper_title: Epinephrine electrochemical sensor based on a carbon paste electrode modified with hydroquinone derivative and graphene oxide nano-sheets: Simultaneous determination of epinephrine, acetaminophen and dopamine

paper_content:

Abstract In this paper, an electrochemical sensor was constructed for determination of epinephrine based on carbon paste electrode (CPE) modified with graphene oxide (GO) and 2-(5-Ethyl-2,4-dihydroxyphenyl)-5,7-dimethyl-4H-pyrido[2,3-d][1,3]thiazine-4-one (EDDPT) as modifiers. The modified electrode was applied as an electrochemical sensor for oxidation of epinephrine (EP). Under the optimum conditions, the over potential of EP oxidation decreased about 279 mV at the modified CPE more than a non-modified CPE. Electrochemical behavior of EP was investigated on the fabricated electrode by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) methods, and some kinetic parameters of EP were obtained, too. The linear range and the detection limit for EP were found to be 1.5–600.0 μM and 0.65 μM (based on 3 s/m), respectively using the EDDPT/GO/CPE sensor and the differential pulse voltammetry (DPV) method. Also, the designed electrochemical sensor was applied to determine EP in the drug sample and simultaneous determination of epinephrine (EP), acetaminophen (AC) and dopamine (DA) in human serum solutions.
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paper_title: Conducting polymer-based electrochemical biosensors for neurotransmitters: A review

paper_content:

Abstract Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.
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paper_title: Electropolymerization of ferulic acid on multi-walled carbon nanotubes modified glassy carbon electrode as a versatile platform for NADH, dopamine and epinephrine separate detection

paper_content:

Abstract The polymerization of ferulic acid (poly-FA) on multi-walled carbon nanotubes (MWCNT) modified glassy carbon electrode was performed and the modified platform applied for the determination of NADH, epinephrine (EP) and dopamine (DA), one at a time. Cyclic voltammetry and chronoamperometry were employed to investigate the electrocatalytic oxidation of NADH, EP and DA on the modified electrode, in aqueous solutions. The obtained analytical curves for NADH, EP, and DA showed linear ranges between 59–1560, 73–1406, and 5–120 μmol L− 1, respectively. The detection limits were 17.7, 22.2 and 2.2 μmol L− 1 for NADH, EP and DA, respectively. The catalytic constant for the oxidation of NADH, EP and DA on the modified electrode were 5.56 × 103, 6.99 × 103 and 1.15 × 104 L mol− 1 s− 1, respectively. The obtained versatile electrode was applied to the successful determination of EP, in epinephrine hydrochloride injection and DA in pharmaceutical samples.
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paper_title: Simultaneous determination of epinephrine and acetaminophen concentrations using a novel carbon paste electrode prepared with 2,2'-[1,2 butanediylbis(nitriloethylidyne)]-bis-hydroquinone and TiO(2) nanoparticles.

paper_content:

A carbon paste electrode (CPE) modified with 2,2'-[1,2 butanediylbis(nitriloethylidyne)]-bis-hydroquinone (BBNBH) and TiO(2) nanoparticles was used for the sensitive voltammetric determination of epinephrine (EP). The electrochemical response characteristics of the modified electrode toward EP and acetaminophen (AC) were investigated by cyclic and differential pulse voltammetry (CV and DPV). The results showed an efficient catalytic activity of the electrode for the electrooxidation of EP, which leads to a reduction in its overpotential by more than 270mV. The effects of pH and potential sweep rate on the mechanism of the electrode process were investigated. The modified electrode exhibits an efficient electron-mediating behavior together with well-separated oxidation peaks for EP and AC. At the optimum pH of 8.0 in a 0.1M phosphate buffer solution, the DPV anodic peak currents showed a linear relationship versus EP concentrations in the range of 1.0-600.0microM and a detection limit of 0.2microM.
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paper_title: Electrochemical monitoring of biogenic amine neurotransmission in real time

paper_content:

Three techniques, constant-potential amperometry, high-speed chronoamperometry, and fast-scan cyclic voltammetry, have been used extensively to investigate the rapid events associated with neurotransmission. These techniques vary in sensitivity, chemical resolution and temporal resolution. Amperometry provides the best temporal resolution but little chemical resolution. Fast-scan cyclic voltammetry provides both good temporal and chemical resolution, while high-speed chronoamperometry offers good temporal resolution and moderate chemical resolution. The amount of chemical information which is needed for a neurochemical measurement depends upon the sample. For single cells, secondary methods, such as HPLC and capillary electrophoresis, offer extensive chemical information about the contents of a cell. With this information, chemical information is not needed during the electrochemical measurement. Therefore, amperometry is employed to obtain the greatest temporal resolution. However, when using more complex biological samples, such as brain slices or in vivo implantation, there is a greater demand for chemical resolution provided by the electrochemical measurement. To bolster results, further confirmation is sought from anatomical, physiological and pharmaceutical evidence. Within this review, the three electrochemical techniques are outlined and compared. Examples are then provided of measurements which have been made in the three predominant biological samples which have been studied: single cells, brain slices and intact animals.
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paper_title: A highly sensitive nanostructure-based electrochemical sensor for electrocatalytic determination of norepinephrine in the presence of acetaminophen and tryptophan.

paper_content:

A new electrochemical sensor for the determination of norepinephrine (NE), acetaminophen (AC) and tryptophan (Trp) is described. The sensor is based on carbon paste electrode (CPE) modified with 3,4-dihydroxybenzaldehyde-2,4-dinitrophenylhydrazone (DDP) and takes the advantages of carbon nanotubes (CNTs), which makes the modified electrode highly sensitive for the electrochemical detection of these compounds. Cyclic voltammetry (CV) at various scan rates was used to investigate the redox properties of the modified electrode. The apparent charge transfer rate constant, k(s), and transfer coefficient, α, for electron transfer between DDP and CNT paste electrode were calculated. The mediated oxidation of NE at the modified electrode was investigated by CV and the values of k, α and diffusion coefficient (D) were calculated. Under the optimum pH of 7.0, the oxidation of NE occurs at a potential about 215 mV less positive than that of the unmodified CPE. Differential pulse voltammetry (DPV) of NE at the modified electrode exhibited two linear dynamic ranges with a detection limit (3σ) of 77±2 nM. DPV was used for simultaneous determination of NE, AC and Trp at the modified electrode, and quantitation of NE in some real samples by the standard addition method.
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paper_title: Ultrasensitive in-vitro monitoring of monoamine neurotransmitters from dopaminergic cells

paper_content:

Abstract The design of biosensing assay of monoamine neurotransmitters (MANTs) such as epinephrine (Ep), norepinephrine (NE), and dopamine (DA), as well as the monitoring of these MANTs released from dopaminergic cells, are of particular interest. Electrochemical sensors based on the novel construction of nickel oxides (NiO) were fabricated and employed for electrochemical screening of MANTs. A novel NiO-lacy flower-like (NLF) geometrical structure with semi-spherical head surfaces connected with a trunk as an arm was achieved. The designed semi-spherical head associated with abundant and the well-dispersed tubular branches with needle-like open ends might lead to the creation of vascular vessels for facile diffusion and suitable accommodation of the released MANTs throughout active and wide-surface-area coverage, multi-diffusive pores, and caves with connective open macro-/meso-windows along the entire top-view nanoneedles of lacy flower head and trunk. These electrode surfaces possess high-index catalytic site facets associated with the formation of ridges/defects on {110}-top-cover surface dominants for strong binding, fast response, and signaling of MANTs. The NLF- modified electrode enabled high sensitivity for MANTs and a low limit of detection of 6 nM. Ultrasensitive in-vitro monitoring of DA released from dopaminergic cells (such as PC12) was realized. The NLF electrode was used to detect MANTs from its sources (PC12), and it could be used for clinical diagnosis.
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paper_title: Nanogold based electrochemical sensor for determination of norepinephrine in biological fluids

paper_content:

Abstract A stable layer of gold nano particles (AuNPs) was deposited on the surface of indium tin oxide (ITO) and was used as an electrode for the detection of norepinephrine (NE) by square wave voltammetry (SWV) and cyclic voltammetry (CV). This modified electrode exhibits potent and persistent electron-mediating behavior and a well-defined oxidation peak towards NE was observed. The peak potential of NE was observed at less positive potential with increase in peak current as compared to bare ITO and bare gold electrodes. NE exhibited two quasi-reversible couples at AuNPs modified ITO over the potential range from −0.6 to 0.8 V in phosphate buffer solution (PBS) (pH 7.2). At optimal experimental condition, the catalytic oxidative peak current was responsive with the NE concentrations ranging from 100 nM to 25 μM. The detection limit was found to be 87 nM. Also, the effect of pH revealed that the oxidation of NE at the AuNPs modified ITO involved the transfer of equal number of protons and electrons. The interfering effect of common coexisting metabolites in blood and urine has also been reported. The modified electrode exhibited high stability and reproducibility. A comparison of results with high performance liquid chromatography (HPLC) signalizes a good agreement.
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paper_title: Continuous and selective measurement of oxytocin and vasopressin using boron-doped diamond electrodes

paper_content:

The electrochemical detection of oxytocin using boron-doped diamond (BDD) electrodes was studied. Cyclic voltammetry of oxytocin in a phosphate buffer solution exhibits an oxidation peak at +0.7 V (vs. Ag/AgCl), which is attributable to oxidation of the phenolic group in the tyrosyl moiety. Furthermore, the linearity of the current peaks obtained in flow injection analysis (FIA) using BDD microelectrodes over the oxytocin concentration range from 0.1 to 10.0 μM with a detection limit of 50 nM (S/N = 3) was high (R2 = 0.995). Although the voltammograms of oxytocin and vasopressin observed with an as-deposited BDD electrode, as well as with a cathodically-reduced BDD electrode, were similar, a clear distinction was observed with anodically-oxidized BDD electrodes due to the attractive interaction between vasopressin and the oxidized BDD surface. By means of this distinction, selective measurements using chronoamperometry combined with flow injection analysis at an optimized potential were demonstrated, indicating the possibility of making selective in situ or in vivo measurements of oxytocin.
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paper_title: Oxytocin increases trust in humans

paper_content:

Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.
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paper_title: Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles

paper_content:

The present study examines the developmental consequences of neonatal exposure to oxytocin on adult social behaviors in female prairie voles (Microtus ochrogaster). Female neonates were injected within 24 h of birth with isotonic saline or one of four dosages of oxytocin (OT). As adults, females were tested in an elevated plus-maze paradigm (a measure of anxiety and exploratory behavior), and for alloparental behavior and partner preferences. At 2 mg/kg OT, females took longer to approach pups, but were the only group to form a statistically significant within-group partner preference. At 4 mg/kg OT, females retrieved pups significantly more frequently but no longer displayed a partner preference; while females treated developmentally with 8 mg/kg spent significantly more time in side-to-side contact with a male stranger than any other treatment group. OT may have broad developmental consequences, but these effects are not linear and may both increase and decrease the propensity to display behaviors such as pair-bonding.
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paper_title: Oxytocin links mothering received, mothering bestowed and adult stress responses.

paper_content:

We review recent discoveries that implicate oxytocin in the intergenerational transmission of similar levels of maternal behavior and acute stress responses in female rats. First, ICV-infused oxytocin antagonist decreased the display by nursing dams of pup-licking (PL) and arched-back nursing (ABN), but not other components of maternal behavior, and increased maternal self-grooming suggesting that oxytocin may shift the balance of oral grooming by dams away from themselves and toward pups. Second, oxytocin receptor concentrations in areas of the adult brain where oxytocin stimulates maternal behavior or diminishes anxiety and adrenal axis responses to acute stress were positively related to PL-ABN received during infancy. Third, oxytocin and oxytocin antagonist treatments of pups on postnatal days 2-10, respectively increased and decreased PL by the treated rats when adult and themselves nursing dams. This indicates that oxytocin activity in female pups, which may be regulated by PL-ABN received from thei...
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paper_title: PEDOT-reduced graphene oxide-silver hybrid nanocomposite modified transducer for the detection of serotonin

paper_content:

Abstract We have developed PEDOT - reduced graphene oxide - silver hybrid nanocomposite (PEDOTNTs/rGO/Ag NPs) modified electrode as a transducer for the detection of serotonin. Structure and properties of the nanocomposites were characterized by XPS, XRD, SEM, TEM, FT-IR, UV–Visible, and Raman spectroscopy. The electrochemical impedance spectroscopic (EIS) results showed a very low charge transfer resistance (198 Ω) for the modified electrode and its sensing performance towards serotonin studied by various electrochemical techniques such as cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry (CA). PEDOTNTs/rGO/AgNPs/GCE showed better performance by DPV with a lower detection limit of 0.1 nM with high operational stability, reproducibility (inter- and intra-electrode - 2.3%) response time (8 s) and sensitivity (14.304 μA mM − 1 /cm 2 ). It also showed a liner range from 1 nM to 0.5 mM (linear regression equation y = 6.33 e − 6 x + 0.153 e − 6 ). The kinetics of serotonin oxidation was studied by chronoamperometry and the catalytic rate constant calculated as 1.647 × 10 3 mol − 1 Ls − 1 . Later, the modified electrode demonstrated as a transducer for the selective detection of serotonin in the presence of ascorbic acid, uric acid and tyrosine. Real sample analysis and interference studies suggested the modified electrode can be exploited in pharmaceutical and medical fields.
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paper_title: Highly selective electrochemical detection of serotonin on polypyrrole and gold nanoparticles-based 3D architecture

paper_content:

Abstract A new customized platform based on electrochemically generated polypyrrole nanoparticles decorated with gold nanoparticles was used for the highly selective and sensitive electrochemical detection of serotonin. The composite surface manifested improved properties attributed to both modifiers: an increased active surface area due to the polypyrrole nanostructure and a catalytic effect towards analyte detection from the noble metal. The material was applied to the detection of serotonin in serum samples, in the presence of interfering species. The analytical performance was 320 times better than that of the bare electrode, underlining the advantages of this tailored hybrid surface.
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paper_title: A novel sensitive sensor for serotonin based on high-quality of AuAg nanoalloy encapsulated graphene electrocatalyst.

paper_content:

A high quality graphene-encapsulated AuAg alloy (AuAg-GR) nanohybrid with homogeneous structure and good reproducibility over a desired area was successfully fabricated. Taking benefits of the unique architecture, such nanohybrid was employed as an efficient electrocatalyst for sensing application. The AuAg-GR based sensor could sensitively detected neurotransmitter serotonin (5-HT) with wide linear detection range (2.7nM to 4.82μM), very low detection limit (1.6nM), negligible interference, and excellent reproducibility. In addition, AuAg-GR based sensor accurately determined 5-HT in human serum samples. This is due to the enhanced catalytic activity of GR nanosheets-encapsulated AuAg nanostructures, which possessed well monodispersion of AuAg alloy, greater electrochemical active sites, and good charge transfer possibility. The obtained results imply that such nanohybrid is a potential candidate for synthesizing electrochemical sensors in requirement of high sensitivity, long-term stability, and good reproducibility.
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paper_title: Immobilization strategies to develop enzymatic biosensors.

paper_content:

Immobilization of enzymes on the transducer surface is a necessary and critical step in the design of biosensors. An overview of the different immobilization techniques reported in the literature is given, dealing with classical adsorption, covalent bonds, entrapment, cross-linking or affinity as well as combination of them and focusing on new original methods as well as the recent introduction of promising nanomaterials such as conducting polymer nanowires, carbon nanotubes or nanoparticles. As indicated in this review, various immobilization methods have been used to develop optical, electrochemical or gravimetric enzymatic biosensors. The choice of the immobilization method is shown to represent an important parameter that affects biosensor performances, mainly in terms of sensitivity, selectivity and stability, by influencing enzyme orientation, loading, mobility, stability, structure and biological activity.
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paper_title: Optimization of enzyme immobilization on functionalized magnetic nanoparticles for laccase biocatalytic reactions

paper_content:

Abstract Magnetic materials can be easily separated from reaction media by application of an external magnetic field. On the other hand, nanomaterials are innovative platforms which present high surface-to-volume ratio allowing low mass transfer limitations. Magnetic nanoparticles (MNPs) can be considered as supports for catalysts immobilization since they greatly improve their reutilization avoiding the need of energy and time consuming centrifugation steps. Enzyme immobilization processes providing high biocatalysts stability are very desirable due to enzyme associated costs. Laccase (EC 1.10.3.2), an oxidative enzyme with numerous industrial applications, requires new technologies for its immobilization in order to improve its biocatalytic activity with reduced costs. In this study, the conditions of laccase immobilization on magnetic nanoparticles were optimised by box-Benhken experimental design. Laccase was successfully bound on functionalized MNPs according to FTIR spectroscopy. At the optimal conditions, the highest recovery activity of immobilized laccase reached 36.3 U/L. Compared to free laccase, thermal stability of immobilized laccase was improved. The immobilized laccase was able to retain above 75% of activity after 6 consecutive cycles of reaction. MNPs can be used for immobilization of important enzymes at industrial level, as these nanomaterials can improve both enzymatic application properties and easy and fast recovery for reutilization.
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paper_title: Recent advances in immobilized enzymes on nanocarriers

paper_content:

Abstract Recent progress in nanotechnology has provided high-performance nanomaterials for enzyme immobilization. Nanobiocatalysts combining enzymes and nanocarriers are drawing increasing attention because of their high catalytic performance, enhanced stabilities, improved enzyme–substrate affinities, and reusabilities. Many studies have been performed to investigate the efficient use of cellulose nanocrystals, polydopamine-based nanomaterials, and synthetic polymer nanogels for enzyme immobilization. Various nanobiocatalysts are highlighted in this review, with the emphasis on the design, preparation, properties, and potential applications of nanoscale enzyme carriers and nanobiocatalysts.
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paper_title: A magnetic biocatalyst based on mussel-inspired polydopamine and its acylation of dihydromyricetin

paper_content:

A support made of mussel-inspired polydopamine-coated magnetic iron oxide nanoparticles (PD-MNPs) was prepared and characterized. The widely used Aspergillus niger lipase (ANL) was immobilized on the PD-MNPs (ANL@PD-MNPs) with a protein loading of 138 mg/g and an activity recovery of 83.6% under optimized conditions. For the immobilization, the pH and immobilization time were investigated. The pH and thermal and storage stability of the ANL@PD-MNPs significantly surpassed those of free ANL. The ANL@PD-MNPs had better solvent tolerance than free ANL. The secondary structure of free ANL and ANL@PD-MNPs was analyzed by infrared spectroscopy. A kinetic study demonstrated that the ANL@PD-MNPs had enhanced enzyme-substrate affinity and high catalytic efficiency. The ANL@PD-MNPs was applied as a biocatalyst for the regioselective acylation of dihydromyricetin (DMY) in DMSO and gave a conversion of 79.3%, which was higher than that of previous reports. The ANL@PD-MNPs retained over 55% of its initial activity after 10 cycles of reuse. The ANL@PD-MNPs were readily separated from the reaction system by a magnet. The PD-MNPs is an excellent support for ANL and the resulting ANL@PD-MNPs displayed good potential for the efficient synthesis of dihydromyricetin-3-acetate by enzymatic regioselective acylation.
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paper_title: Sensors and biosensors based on magnetic nanoparticles

paper_content:

Abstract Magnetic nanoparticles (MNPs) have attracted a growing interest in the development and fabrication of sensors and biosensors for several applications. MNPs can be integrated into the transducer materials and/or be dispersed in the sample followed by their attraction by an external magnetic field onto the active detection surface of the (bio)sensor. This review describes and discusses the recent applications of MNPs in sensors and biosensors, taking into consideration their analytical figures of merit. This work also addresses the future trends and perspectives of sensors and biosensors based on MNPs.
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paper_title: Carbon Paste Electrodes in Facts, Numbers, and Notes: A Review on the Occasion of the 50-Years Jubilee of Carbon Paste in Electrochemistry and Electroanalysis

paper_content:

This article reviews the electrochemistry and electroanalytical applications of carbon paste-based electrodes, sensors, and detectors on the occasion of the half-of-century anniversary since the discovery of carbon paste. The review (with 333 references) has been prepared in the form of a retrospective compilation presenting the field by means of various facts, notes, data, surveys, and summaries, including numerous rarities or curiosities that illustrate the individual achievements and milestones. Carbon paste-based electrodes are discussed in their entirety by covering all important areas of the field, starting from basic characterization of carbon paste as the electrode material, via its typical physicochemical and electrochemical properties or specific features, up to a representative documentation of their applicability in electrochemical and electroanalytical measurements.
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paper_title: Recent advances in cholesterol biosensor.

paper_content:

Biosensors have recently gained much attention in the field of health care for the management of various important analytes in a biological system. The area achieved tremendous progress from the time when the first Clark electrode for measurement of glucose was realized. Advances in the biosensor design are appearing at a high rate as these devices play increasingly important roles in our daily lives. The increasing incidences of cardiovascular diseases and cardiac arrest are major cause of death of humans world over. One of the most important reasons is hypercholesterolemia, i.e. increased concentration of cholesterol in blood. Hence estimation of cholesterol level in blood is important in clinical applications. This review aims to highlight the recent advances in materials and techniques for cholesterol biosensor design and construction.
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paper_title: Preparation of a Three-Dimensional Reduced Graphene Oxide Film by Using the Langmuir–Blodgett Method

paper_content:

The Langmuir-Blodgett method has always been traditionally utilized in the deposition of two-dimensional structures. In this work, however, we employed the method to deposit three-dimensional reduced graphene oxide layers using an unconventional protocol for the first time. This was achieved by carrying out the dipping process after the collapse pressure or breaking point, which results in the formation of a highly porous three-dimensional surface topography. By varying the number of deposition layers, the porosity could be optimized from nanometer to micrometer dimensions. Employed as bioelectrodes, these three-dimensional reduced graphene oxide layers may allow improved adhesion and biocompatibility compared to the conventional two-dimensional surfaces. A larger number of pores also improves the mass transport of materials and therefore increases the charge-sustaining capacity and sensitivity. This could ultimately improve the performance of biofuel cells and other electrode-based systems.
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paper_title: Enzymatic detection of heavy metal ions in aqueous solution from vegetable wastes by immobilizing pumpkin (Cucumis melo) urease in calcium alginate beads

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Enzyme urease is extracted from the discarded seeds of pumpkin. Urease was purified to apparent homogeneity (5.2 fold) by heat treatment at 48 ± 1°C and gel filtration through Sephadex G-200. Effect of model metal ions on the activity of the homogeneous enzyme preparation (sp. activity 353 U/mg protein, A280/A260 = 1.12) of soluble as well as immobilized enzyme was investigated. The soluble and immobilized urease has been used for the quantitative estimation of general water pollution with heavy metal ions like Hg2+, Cu2+, Cd2+, and Co2+. The measurements of the urease residual activity have been carried out in tris-acetate buffer after pre-incubation of model metal salt. The inhibition was found to be biphasic with an initial rapid loss of activity and remainder in slow phase of 10∼15 min. The immobilization was done in 3.5% alginate beads leading to 86% of entrapment. There was no leaching of the enzyme over a period of 15 days at 4°C. The beads were fairly stable up to 50°C and exhibited activity even at −10°C. The inhibition by these ions was non-competitive and irreversible, hence could not be restored by dialysis. Based on the values of inhibition constant Ki the heavy-metal ions were found to inhibit urease in the following order Hg2+ > Cu2+ > Cd2+ > Co2+.
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paper_title: Development of electrochemical biosensor based on tyrosinase immobilized in composite biopolymeric film.

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Abstract An electrochemical enzyme electrode for dopa and dopamine was developed via an easy and effective immobilization method. The enzyme tyrosinase was extracted from a plant source Amorphophallus companulatus and immobilized in a novel composite of two biopolymers: agarose and guar gum. This composite matrix-containing enzyme forms a self-adhering layer on the active surface of glassy carbon electrode, making it a selective and sensitive phenol sensor. Dopa and dopamine were determined by the direct reduction of biocatalytically liberated quinone species at −0.18 V versus Ag/AgCl (3 M KCl). The analytical characteristics of this sensor, including linear range, lower detection limit, pH, and storage stability, are described. It has reusability up to 15 cycles and a shelf life of more than 2 months.
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paper_title: Progress in Enzyme-Based Biosensors Using Optical Transducers

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Enzyme-based biosensors are well developed and relatively mature technique in the biosensing field. Biosensors that utilise enzymes as the recognition elements represent the most extensively studied area. The organisation of an enzyme-based biosensor requires the integration of the biocatalyst with the support or immobilised materials to the extent that the biocatalytic transformation is either optically or electronically transduced. Any optical or electrical changes at the support material as a result of the biocatalytic process, that is, depletion of the reactant or formation of the product, provide routes for the opto/electronic transduction of the biological process occurring at the sensing surface. This review focuses on the discussion of some enzyme immobilisation techniques including physical and chemical immobilisation. Enzyme-based biosensors using various optical detection methods such as absorptiometry, luminometry, chemiluminescence, evanescent wave, and surface plasmon resonance are also included. Finally, different types of enzyme-based optical biosensors for ascorbic acid, bilirubin, cholesterol, choline, ethanol, glucose, glutamate/glutamine, lactate, penicillin, urea, and uric acid determinations are presented.
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paper_title: New electrochemiluminescent biosensors combining polyluminol and an enzymatic matrix

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Performant reagentless electrochemiluminescent (ECL) (bio)sensors have been developed using polymeric luminol as the luminophore. The polyluminol film is obtained by cyclic voltammetry (CV) on a screen-printed electrode either in a commonly used H2SO4 medium or under more original near-neutral buffered conditions. ECL responses obtained after performing polymerization either at acidic pH or at pH 6 have been compared. It appears that polyluminol formed in near-neutral medium gives the best responses for hydrogen peroxide detection. Polymerization at pH 6 by cyclic voltammetry gives a linear range extending from 8 × 10−8 to 1.3 × 10−4 M H2O2 concentrations. Based on this performant sensor for hydrogen peroxide detection, an enzymatic biosensor has been developed by associating the polyluminol film with an H2O2-producing oxidase. Here, choline oxidase (ChOD) has been chosen as a model enzyme. To develop the biosensor, luminol has been polymerized at pH 6 by CV, and then an enzyme-entrapping matrix has been formed on the above modified working electrode. Different biological (chitosan, agarose, and alginate) and chemical (silica gels, photopolymers, or reticulated matrices) gels have been tested. Best performances have been obtained by associating a ChOD-immobilizing photopolymer with the polyluminol film. In this case, choline can be detected with a linear range extending from 8 × 10−8 to 1.3 × 10−4 M.
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paper_title: Immobilization of enzymes: a literature survey.

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The term immobilized enzymes refers to "enzymes physically confined or localized in a certain defined region of space with retention of their catalytic activities, and which can be used repeatedly and continuously." Immobilized enzymes are currently the subject of considerable interest because of their advantages over soluble enzymes. In addition to their use in industrial processes, the immobilization techniques are the basis for making a number of biotechnology products with application in diagnostics, bioaffinity chromatography, and biosensors. At the beginning, only immobilized single enzymes were used, after 1970s more complex systems including two-enzyme reactions with cofactor regeneration and living cells were developed. The enzymes can be attached to the support by interactions ranging from reversible physical adsorption and ionic linkages to stable covalent bonds. Although the choice of the most appropriate immobilization technique depends on the nature of the enzyme and the carrier, in the last years the immobilization technology has increasingly become a matter of rational design. As a consequence of enzyme immobilization, some properties such as catalytic activity or thermal stability become altered. These effects have been demonstrated and exploited. The concept of stabilization has been an important driving force for immobilizing enzymes. Moreover, true stabilization at the molecular level has been demonstrated, e.g., proteins immobilized through multipoint covalent binding.
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paper_title: Immobilization of cellulase enzyme onto magnetic nanoparticles: Applications and recent advances

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Abstract Among the industrial enzymes, cellulase plays a central role in biotechnology and agricultural applications such as foods, chemicals, detergents, cosmetics, pulp, and paper. Most of these applications suffer from low thermal and storage stability of cellulase, contamination of products by enzyme and lake of enzyme reusability that make process inappropriate in economic viewpoint. For overcoming these issues and improve the stability and reusability of the enzyme, the immobilization methods could employ. Recently, the immobilization of cellulase on nanomaterials is under more considerable attention due to the significant surface properties of these supports. However, the application of these supports is also restricted by troubles in recovery, e.g., via centrifugation or filtration. This restriction could be solved using magnetic nanoparticles (MNPs) that can simply separate from the reaction media by using a simple magnet. MNPs have been commonly used for enzyme immobilization in recent years due to this practical advantage and their low toxicity. In this review, we attempt to provide a more detailed overview of the applications and recent advances of immobilization of cellulase enzyme onto different functionalized MNPs. At last, we tried to present the future perspective of this research area such as the enzyme reusability, the facile recovery way of cellulase, and the efficient biotechnology production process.
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paper_title: Optical biochemical sensor for determining hydroperoxides in nonpolar organic liquids as archetype for sensors consisting of amphiphilic conetworks as immobilisation matrices

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This paper reports the successful design of a prototype of an optical biochemical sensor for the determination of hydroperoxides in nonpolar organic liquids. The sensor consists of a matrix of an amphiphilic polymer conetwork (APCN), a novel class of very promising polymeric materials for easy preparation of biochemical sensor matrices. APCNs are characterised by nanoscopic phase separation between the hydrophilic and the hydrophobic phases. For medium ratios of conetwork composition, the domains of both phases are interconnected both on the surface of the conetworks and throughout the bulk. The APCNs have peculiar swelling properties—the hydrophilic phase swells in hydrophilic media and the hydrophobic phase swells in hydrophobic media. In both types of media dissolved reagents can diffuse from the solution into the swollen phase of the polymeric conetwork. This enables loading of the hydrophilic phase of the APCNs with enzymes and indicator reagents by simple impregnation. Hydrophobic analytes can diffuse into the polymeric conetwork via its hydrophobic phase and react with indicator reagents immobilised in the hydrophilic phase at the huge internal interface between the two opposite phases.
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paper_title: Twenty years research in cholinesterase biosensors: from basic research to practical applications.

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Over the last decades, cholinesterase (ChE) biosensors have emerged as an ultra sensitive and rapid technique for toxicity analysis in environmental monitoring, food and quality control. These systems have the potential to complement or replace the classical analytical methods by simplifying or eliminating sample preparation protocols and making field testing easier and faster with significant decrease in costs per analysis. Over the years, engineering of more sensitive ChE enzymes, development of more reliable immobilization protocols and progress in the area of microelectronics could allow ChE biosensors to be competitive for field analysis and extend their applications to multianalyte screening, development of small, portable instrumentations for rapid toxicity testing, and detectors in chromatographic systems. In this paper, we will review the research efforts over the last 20 years in fabricating AChE biosensors and the recent trends and challenges encounter once the sensor is used outside research laboratory for in situ real sample applications. The review will discuss the generations of cholinesterase sensors with their advantages and limitations, the existing electrode configurations and fabrication techniques and their applications for toxicity monitoring. We will focus on low-cost electrochemical sensors and the approaches used for enzyme immobilization. Recent works for achieving high sensitivity and selectivity are also discussed.
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paper_title: Entrapment of biomolecules in sol–gel matrix for applications in biosensors: Problems and future prospects

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Abstract An emerging area that has attracted increased attention in recent years is the development of biosensors based on sol–gel-derived platforms which must be predicated on an understanding of the short and long-term interactions between the biorecognition elements and evolving sol–gel matrix. This review focuses on the growing field of entrapment of biomolecules such as proteins, enzymes and antibodies in sol–gel matrices prepared from alkoxide precursors. Basic aspects of sol–gel, its advantages and disadvantages, factor affecting the sol–gel-derived thin films, strategies for improving entrapment of biomolecules in sol–gel materials and their organic modifications are discussed. Organically modified silane precursors have the ability to tune physical and chemical properties with desired characteristics of sol–gel preparations by simply changing different precursors and their molar ratio. The usefulness of optical method especially time-resolved fluorescence spectroscopy for the characterization of internal environment of sol–gel as well as dynamics of proteins within the sol–gel is highlighted. Significance and designing of new biocompatible sol–gel precursors with the purpose of making the glassy matrix more compatible with entrapped biomolecules has been described. Considerable attention has been drawn on problems and future prospects of sol–gel matrix for entrapment of biomolecules for applications in biosensors.
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paper_title: Immobilization of enzymes on clay minerals for biocatalysts and biosensors

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Abstract Many studies suggest that naturally-occurring layered clay minerals can be used as a class of biocompatible solid supports for immobilizing enzymes. The corresponding clay mineral enzyme hybrids prove to have great potentials in catalysis and biosensing. This article reviews latest advances in using clay minerals as supports for the immobilization of enzymes. The immobilization of enzyme onto clay minerals can be made via non-covalent adsorption and covalent bonding. The non-covalent immobilization involves van der Waals forces, electrostatic interactions, hydrogen bonding, and hydrophobic interactions. For avoiding desorption of enzymes, immobilization can be conducted through direct covalent bonding between enzymes and clay minerals. Organic modification of clay minerals and addition of linking molecules are made to improve the immobilization so as to increase the loading, activity and stability of enzymes. Regarding the applications of enzyme immobilized on clay minerals, recent studies are made mainly in biocatalytic processes and in biosensors. For manufacturing biosensing electrodes, clay minerals with metal nanoparticles, graphene and carbon nanotubes prove to be more effective owing mainly to the enhanced electron transfer. Future work on clay mineral enzyme hybrids could lie in integrating more additional functional materials with clay mineral enzyme hybrids to build hierarchical structured catalysts and electrodes.
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paper_title: Highly selective electrochemical detection of serotonin on polypyrrole and gold nanoparticles-based 3D architecture

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Abstract A new customized platform based on electrochemically generated polypyrrole nanoparticles decorated with gold nanoparticles was used for the highly selective and sensitive electrochemical detection of serotonin. The composite surface manifested improved properties attributed to both modifiers: an increased active surface area due to the polypyrrole nanostructure and a catalytic effect towards analyte detection from the noble metal. The material was applied to the detection of serotonin in serum samples, in the presence of interfering species. The analytical performance was 320 times better than that of the bare electrode, underlining the advantages of this tailored hybrid surface.
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paper_title: Preparation and Characterization of Immobilized Lipase from Pseudomonas Cepacia onto Magnetic Cellulose Nanocrystals

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Magnetic cellulose nanocrystals (MCNCs) were prepared and used as an enzyme support for immobilization of Pseudomonas cepacialipase (PCL). PCL was successfully immobilized onto MCNCs (PCL@MCNC) by a precipitation-cross-linking method. The resulting PCL@MCNC with a nanoscale size had high enzyme loading (82.2 mg enzyme/g) and activity recovery (95.9%). Compared with free PCL, PCL@MCNC exhibited significantly enhanced stability and solvent tolerance, due to the increase of enzyme structure rigidity. The observable optimum pH and temperature for PCL@MCNC were higher than those of free PCL. PCL@MCNC manifested relatively higher enzyme-substrate affinity and catalytic efficiency. Moreover, PCL@MCNC was capable of effectively catalyzing asymmetric hydrolysis of ketoprofenethyl ester with high yield of 43.4% and product e.e. of 83.5%. Besides, immobilization allowed PCL@MCNC reuse for at least 6 consecutive cycles retaining over 66% of its initial activity. PCL@MCNC was readily recycled by magnetic forces. Remarkably, the as-prepared nanobiocatalyst PCL@MCNC is promising for biocatalysis.
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paper_title: Biocompatible cellulose nanocrystals as supports to immobilize lipase

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Abstract Cellulose nanocrystals (CNCs) are rod-like cellulose nanomaterials that can be economically prepared from various cellulosic materials by the elimination of amorphous regions of cellulose. CNCs can be used as supports to immobilize enzymes because of their inherent biocompatibility, high specific-surface area, and exceptional mechanical properties. In this study, CNCs obtained from cotton linter cellulose (CLC) and bacterial cellulose (BC) were used as supports to immobilize Candida rugosa lipase. The protein loading and immobilization yield of the lipase immobilized onto the CNC obtained from CLC (CNC⿿CLC) were 1.8 and 2.2 times higher, respectively, than those of the lipase immobilized onto CLC. The lipase immobilized onto CNC⿿CLC showed significantly enhanced thermal stability. The half-life time of the immobilized lipase during incubation at 60 °C was 27 times higher than that of free lipase. The lipase immobilized onto CNC⿿CLC also showed increased pH stability at an alkaline pH. The residual activity of the immobilized lipase after 5 h incubation at pH 10 was 8.8 times higher than that of free lipase. In addition, the lipase immobilized onto CNC⿿CLC was able to perform homogeneous-like biocatalysis without shaking or agitation because the immobilized lipase remained well-dispersed during the aqueous reaction. The CNCs as enzyme supports have many potential applications in the biomedical, bioelectronic, and biocatalytic fields.
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paper_title: Salivary biomarkers detection: Analytical and immunological methods overview

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Abstract Saliva is a complex matrix that reflects hormonal, immunological, metabolic and nutritional state of a person. Moreover, it is considered the most appropriate biological fluid for scientific investigations regarding ethics. Saliva chemistry is an emerging field and mostly employed in toxicology and forensic medicine for analysing and detecting user drug addiction and alcohol abuse by mapping the blood and saliva data. The advantages of salivary testing include helping in the diagnosis, prognosis and surveillance of disease, alongside with the non-invasive and ease of collection properties. The need for fast, cost-effective and reliable methods for saliva investigation has led to high technological advances in developing sensing tools. Hence, increasing number of papers are reporting diseases signalling salivary biomarkers for local or systemic pathologies like oral cancer, endocrine and immunologic pathologies, infectious and neurological diseases etc. This review focuses on the recent advances and main challenges employed in the detection and quantification of salivary biomarkers by separation, immunological and electrochemical techniques and highlight the future perspectives of the point-of-care devices in diagnosing local or systemic pathologies.
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paper_title: Acetylcholinesterase-based biosensors for quantification of carbofuran, carbaryl, methylparaoxon, and dichlorvos in 5% acetonitrile.

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Amperometric acetylcholinesterase biosensors have been developed for quantification of the pesticides carbofuran, carbaryl, methylparaoxon, and dichlorvos in phosphate buffer containing 5% acetonitrile. Three different biosensors were built using three different acetylcholinesterase (AChE) enzymes-AChE from electric eel, and genetically engineered (B394) and wild-type (B1) AChE from Drosophila melanogaster. Enzymes were immobilized on cobalt(II) phthalocyanine-modified electrodes by entrapment in a photocrosslinkable polymer (PVA-AWP). Each biosensor was tested against the four pesticides. Good operational stability, immobilisation reproducibility, and storage stability were obtained for each biosensor. The best detection limits were obtained with the B394 enzyme for dichlorvos and methylparaoxon (9.6 x 10(-11) and 2.7 x 10(-9) mol L(-1), respectively), the B1 enzyme for carbofuran (4.5 x 10(-9) mol L(-1)), and both the B1 enzyme and the AChE from electric eel for carbaryl (1.6 x 10(-7) mol L(-1)). Finally, the biosensors were used for the direct detection of the pesticides in spiked apple samples.
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paper_title: Biosensors and their applications – A review

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Abstract The various types of biosensors such as enzyme-based, tissue-based, immunosensors, DNA biosensors, thermal and piezoelectric biosensors have been deliberated here to highlight their indispensable applications in multitudinous fields. Some of the popular fields implementing the use of biosensors are food industry to keep a check on its quality and safety, to help distinguish between the natural and artificial; in the fermentation industry and in the saccharification process to detect precise glucose concentrations; in metabolic engineering to enable in vivo monitoring of cellular metabolism. Biosensors and their role in medical science including early stage detection of human interleukin-10 causing heart diseases, rapid detection of human papilloma virus, etc. are important aspects. Fluorescent biosensors play a vital role in drug discovery and in cancer. Biosensor applications are prevalent in the plant biology sector to find out the missing links required in metabolic processes. Other applications are involved in defence, clinical sector, and for marine applications.
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paper_title: Biosensing applications of clay-modified electrodes: a review

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Two-dimensional layered inorganic solids, such as cationic clays and layered double hydroxides (LDHs), also defined as anionic clays, have open structures which are favourable for interactions with enzymes and which intercalate redox mediators. This review aims to show the interest in clays and LDHs as suitable host matrices likely to immobilize enzymes onto electrode surfaces for biosensing applications. It is meant to provide an overview of the various types of electrochemical biosensors that have been developed with these 2D layered materials, along with significant advances over the last several years. The different biosensor configurations and their specific transduction procedures are discussed.
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paper_title: Improvement of enzyme activity, stability and selectivity via immobilization techniques

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Abstract In spite of their excellent catalytic properties, enzyme properties have to be usually improved before their implementation at industrial scale (where many cycles of high yield processes are desired). Generally, soluble enzymes have to be immobilized to be reused for long times in industrial reactors and, in addition to that, some other critical enzyme properties have to be improved like stability, activity, inhibition by reaction products, selectivity towards non-natural substrates. Some strategies to improve these enzyme properties during the performance of tailor-made enzyme immobilization protocols are here reviewed. In this way, immobilized enzymes may also exhibit much better functional properties than the corresponding soluble enzymes by very simple immobilization protocols. For example, multipoint and multisubunit covalent immobilization improve the stability of monomeric or multimeric enzymes. Moreover, enantioselectivity of different enzymes (e.g., lipases) may be also dramatically improved (from E = 1 to >100) by performing different immobilization protocols of the same enzyme. In all cases, enzyme engineering via immobilization techniques is perfectly compatible with other chemical or biological approaches to improve enzyme functions and the final success depend on the availability of a wide battery of immobilization protocols.
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paper_title: A novel sensitive sensor for serotonin based on high-quality of AuAg nanoalloy encapsulated graphene electrocatalyst.

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A high quality graphene-encapsulated AuAg alloy (AuAg-GR) nanohybrid with homogeneous structure and good reproducibility over a desired area was successfully fabricated. Taking benefits of the unique architecture, such nanohybrid was employed as an efficient electrocatalyst for sensing application. The AuAg-GR based sensor could sensitively detected neurotransmitter serotonin (5-HT) with wide linear detection range (2.7nM to 4.82μM), very low detection limit (1.6nM), negligible interference, and excellent reproducibility. In addition, AuAg-GR based sensor accurately determined 5-HT in human serum samples. This is due to the enhanced catalytic activity of GR nanosheets-encapsulated AuAg nanostructures, which possessed well monodispersion of AuAg alloy, greater electrochemical active sites, and good charge transfer possibility. The obtained results imply that such nanohybrid is a potential candidate for synthesizing electrochemical sensors in requirement of high sensitivity, long-term stability, and good reproducibility.
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paper_title: Do copper ions activate tyrosinase enzyme? A biosensor model for the solution.

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Some metal ions play a cofactor role for the activity of tyrosinase enzyme and one of them is copper ion. In this study an amperometric biosensor was developed in order to investigate the effect of the copper ions on the activity of tyrosinase enzyme. In the construction of the biosensor tyrosinase enzyme was immobilized on a Clark-type dissolved oxygen probe which was covered with a oxygen sensitive teflon membrane, by using a chemical covalent immobilization method based on gelatine and bifunctional reagent, glutaraldehyde. The principle of the measurement was based on the determination of the differentiation of dissolved oxygen level in the enzymatic reaction catalyzed by tyrosinase in the absence and the presence of copper ions. Differences between the dissolved oxygen concentrations were related to copper ion concentration which was added in to the reaction medium. The biosensor response depends linearly on copper ion concentration between 2.5-20.0microM with a response time 1min. The detection limit of the biosensor is 0.95microM. In the optimization studies of the biosensor, the most suitable amounts of tyrosinase, gelatin and glutaraldehyde ratio were determined to be 69.0U/cm(-2), 4.21mg/cm(-2), and 2.5%, respectively. In the optimization studies of the biosensor, phosphate buffer (pH 7.0 ,50mM) and 30 degrees C were detected to be working conditions. For the characterization of the biosensor some parameters such as reproducibility, thermal and pH stability were carried out.
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paper_title: Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system

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Nicotinic receptors - a family of ligand-gated ion channels that mediate the effects of the neurotransmitter acetylcholine - are among the most well understood allosteric membrane proteins from a structural and functional perspective. There is also considerable interest in modulating nicotinic receptors to treat nervous-system disorders such as Alzheimer's disease, schizophrenia, depression, attention deficit hyperactivity disorder and tobacco addiction. This article describes both recent advances in our understanding of the assembly, activity and conformational transitions of nicotinic receptors, as well as developments in the therapeutic application of nicotinic receptor ligands, with the aim of aiding novel drug discovery by bridging the gap between these two rapidly developing fields.
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paper_title: Detection of Ca2+-induced acetylcholine released from leukemic T-cells using an amperometric microfluidic sensor.

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A microfluidic structured-dual electrodes sensor comprising of a pair of screen printed carbon electrodes was fabricated to detect acetylcholine, where one of them was used for an enzyme reaction and another for a detection electrode. The former was coated with gold nanoparticles and the latter with a porous gold layer, followed by electropolymerization of 2, 2:5,2-terthiophene-3-(p-benzoic acid) (pTTBA) on both the electrodes. Then, acetylcholinesterase was covalently attached onto the reaction electrode, and hydrazine and choline oxidase were co-immobilized on the detection electrode. The layers of both modified electrodes were characterized employing voltammetry, field emission scanning electron microscopy, X-ray photoelectron spectroscopy, and quartz crystal microscopy. After the modifications of both electrode surfaces, they were precisely faced each other to form a microfluidic channel structure, where H2O2 produced from the sequential enzymatic reactions was reduced by hydrazine to obtain the analytical signal which was analyzed by the detection electrode. The microfluidic sensor at the optimized experimental conditions exhibited a wide dynamic range from 0.7nM to 1500μM with the detection limit of 0.6 ± 0.1nM based on 3s (S/N = 3). The biomedical application of the proposed sensor was evaluated by detecting acetylcholine in human plasma samples. Moreover, the Ca2+-induced acetylcholine released in leukemic T-cells was also investigated to show the in vitro detection ability of the designed microfluidic sensor. Interference due to the real component matrix were also studied and long term stability of the designed sensor was evaluated. The analytical performance of the designed sensor was also compared with commercially available ACh detection kit.
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paper_title: Detection of Acetylcholine Receptor Modulating Antibodies by Flow Cytometry

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Objectives: Detection of acetylcholine receptor (AChR) blocking antibodies through the use of a radiolabel has become standard procedure in most laboratories. Known drawbacks associated with radioassay, including cost of radioisotopes, hazards to laboratory professionals, and manufacture and disposal of radioactive materials, have prompted investigation into replacement assays. We describe here a high-throughput immunofluorescent flow cytometric assay designed for the detection of AChR blocking antibodies. Methods: In total, 323 serum samples were tested on both the AChR blocking radioassay and the new immunofluorescent flow cytometric assay. Results: Analysis of the results revealed a 96.9% concordance between the two assay methods. Conclusions: Our results indicate that a new immunofluorescent flow cytometric AChR blocking antibody assay is not only feasible but clinically comparable in both sensitivity (91%) and specificity (99%) compared with radioassay. Myasthenia gravis (MG) is a neuromuscular autoimmune disease primarily associated with the presence of antibodies directed toward receptors embedded in the motor endplate at the neuromuscular junction (NMJ). These antibodies cause blockage, dysfunction, and degradation of acetylcholine receptor (AChR), leading to muscle weakness and fatigability. Three main types of AChR antibodies have been identified and are referred to as binding, modulating, and blocking. These three antibodies are classified based on their different effector mechanisms. AChR binding antibody causes binding and activation of complement at the NMJ. Modulating AChR antibodies cause accelerated degradation of AChR molecules that have been cross-linked by the antibody, a process also referred to as antigenic modulation. Last, the AChR blocking antibody causes functional blocking of the acetylcholine (ACh) binding site. 1 Blocking antibodies render AChR inoperable due to the functional blockage caused by antibody binding at the normal ACh ligand binding site. This mechanism of AChR disruption is less commonly demonstrable in vitro than binding and modulating of receptors; however, in rodent studies, the administration of blocking antibodies causes an acute and severe form of muscle weakness in the absence of either inflammation or necrosis of the NMJ. 2
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paper_title: Towards timely Alzheimer diagnosis: A self-powered amperometric biosensor for the neurotransmitter acetylcholine.

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Serious brain disorders, such as the Alzheimer's Disease (AD), are associated with a marked drop in the levels of important neurotransmitters, such as acetylcholine (ACh). Real time monitoring of such biomarkers can therefore play a critical role in enhancing AD therapies by allowing timely diagnosis, verifications of treatment effectiveness, and developments of new medicines. In this study, we present the first acetylcholine/oxygen hybrid enzymatic fuel cell for the self-powered on site detection of ACh in plasma, which is based on the combination of an enzymatic anode with a Pt cathode. Firstly, an effective acetylcholinesterase immobilized electrode was developed and its electrochemical performance evaluated. Highly porous gold was used as the electrode material, and the enzyme was immobilized via a one step rapid and simple procedure that does not require the use of harsh chemicals or any electrode/enzyme pre-treatments. The resulting enzymatic electrode was subsequently used as the anode of a miniature flow-through membrane-less fuel cell and showed excellent response to varying concentrations of ACh. The peak power generated by the fuel cell was 4nW at a voltage of 260mV and with a current density of 9μAcm-2. The limit of detection of the fuel cell sensor was 10μM, with an average response time as short as 3min. These exciting results open new horizons for point-of-care Alzheimer diagnosis and provide an attractive potential alternative to established methods that require laborious and time-consuming sample treatments and expensive instruments.
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paper_title: Fabrication of an amperometric acetylcholine esterase-choline oxidase biosensor based on MWCNTs-Fe(3)O(4)NPs-CS nanocomposite for determination of acetylcholine

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Abstract In this paper, a novel amperometric bienzymatic biosensor based on iron (II, III) oxide nanoparticles (Fe 3 O 4 NPs), multi-walled carbon nanotubes (MWCNTs) and chitosan (CS) modified glassy carbon electrode (GCE) was fabricated for the determination of acetylcholine (ACh). The CS was used to immobilize acetylcholine esterase (AChE) and choline oxidase (ChOx). The nanocomposites of Fe 3 O 4 NPs and MWCNTs were characterized by scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electrochemical measurements were based on the detection of enzymatically produced hydrogen peroxide (H 2 O 2 ). The experimental parameters such as working potential, enzyme unit, pH and temperature were optimized. The linear ranges of the biosensor were 0.02 μmol L − 1 –0.111 μmol L − 1 and 0.111 μmol L − 1 –1.87 μmol L − 1 . The detection limit was calculated as 0.61 nmol L − 1 . In addition, the amperometric biosensor showed high sensitivity, good selectivity, repeatability, reproducibility and long-term stability. The fabricated biosensor was used to determine ACh levels in serum samples.
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paper_title: Noradrenergic Modulation of Dopamine Transmission Evoked by Electrical Stimulation of the Locus Coeruleus in the Rat Brain.

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Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc). For this study, catecholamine release in the NAc and VTA evoked by electrical stimulation of the LC in urethane-anesthetized rats was simultaneously monitored with carbon-fiber microelectrodes using in vivo multichannel fast-scan cyclic voltammetry for comparison of its extracellular regulation. Pharmacological, anatomical, and electrochemical evidence suggest that electrical stimulation of the LC evokes NE release in the VTA and activates VTA-DA neurons, resulting in DA release in the NAc. The electrically evoked DA in the NAc was regulated by D2 receptors and DA transporters (DAT) as well as α1-adrenergic receptors in the VTA, whereas NE release in the VTA was regulated by α2-adrenergic receptors and NE transporters (NET) not by D2 receptors or DAT. These results suggest that electrical stimulation of LC modulates VTA-DA neurons and DA transmission in the NAc via NE receptors.
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paper_title: Clinical implications and electrochemical biosensing of monoamine neurotransmitters in body fluids, in vitro, in vivo, and ex vivo models

paper_content:

Monoamine neurotransmitters (MNTs) belong to one of the most important groups of neurotransmitters in the central nervous system. They play crucial role in functioning of cardiovascular, renal, and hormonal systems along with establishing human brain-body integration. Abnormal level of MNT is associated with numerous psychotic (schizophrenia, depression, dementia, etc.) and neurodegenerative diseases (Alzheimer's, Parkinson's, Huntington's disease, etc.), therefore their sensitive and robust detection is of great clinical significance. Electrochemical detection (ECD) techniques have been paving the path in this direction, for more than four decades now. Keeping the immense importance of MNTs in mind, this review has been formulated to describe fundamentals of MNTs followed by their clinical significance in neuroscience. Herein, we have emphasized on the ECD of MNTs, in various matrices reported till date. In order to provide information on ECD of MNTs in clinically comparable systems, we have included a comprehensive discussion on sensor design and its analytical performance towards analyzing MNTs in the in vitro, in vivo, and ex vivo models. An extensive table is also incorporated to provide better understanding of the role of MNTs in various clinical conditions. Furthermore, this review briefly discusses the challenges faced with EC sensing techniques and loopholes present in current research works. Apart from this, three extended tables are also included in this review, to provide an insight into the amount of work done in ECD of MNTs in last ten years (2008-2018). These tables comprehensively discuss sensor fabrication strategies for determining MNTs in various matrices and models along with their mode of detection and analytical performance.
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paper_title: Facile fabrication of flexible glutamate biosensor using direct writing of platinum nanoparticle-based nanocomposite ink

paper_content:

Abstract Glutamate excitotoxicity is a pathology in which excessive glutamate can cause neuronal damage and degeneration. It has also been linked to secondary injury mechanisms in traumatic spinal cord injury. Conventional bioanalytical techniques used to characterize glutamate levels in vivo, such as microdialysis, have low spatiotemporal resolution, which has impeded our understanding of this dynamic event. In this study, we present an amperometric biosensor fabricated using a simple direct ink writing technique for the purpose of in vivo glutamate monitoring. The biosensor is fabricated by immobilizing glutamate oxidase on nanocomposite electrodes made of platinum nanoparticles, multi-walled carbon nanotubes, and a conductive polymer on a flexible substrate. The sensor is designed to measure extracellular dynamics of glutamate and other potential biomarkers during a traumatic spinal cord injury event. Here we demonstrate good sensitivity and selectivity of these rapidly prototyped implantable biosensors that can be inserted into a spinal cord and measure extracellular glutamate concentration. We show that our biosensors exhibit good flexibility, linear range, repeatability, and stability that are suitable for future in vivo evaluation.
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paper_title: Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes

paper_content:

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo.
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paper_title: Development of a novel micro biosensor for in vivo monitoring of glutamate release in the brain

paper_content:

Abstract L- Glutamate is the main excitatory neurotransmitter in the central nervous system and hyperglutamatergic signaling is implicated in neurological and neurodegenerative diseases. Monitoring glutamate with a glutamate oxidase-based amperometric biosensor offers advantages such as high spatial and high temporal resolution. However, commercially-available glutamate biosensors are expensive and larger in size. Here, we report the development of 50 µm diameter biosensor for real-time monitoring of L-glutamate in vivo. A polymer, poly-o-phenylenediamine (PPD) layer was electropolymerized onto a 50 µm Pt wire to act as a permselective membrane. Then, glutamate oxidase entrapped in a biocompatible chitosan matrix was cast onto the microelectrode surface. Finally, ascorbate oxidase was coated to eliminate interferences from high levels of extracellular ascorbic acid present in brain tissue. L-glutamate measurements were performed amperometrically at an applied potential of 0.6 V vs Ag/AgCl. The biosensor exhibited a linear range from 5 to 150 μM, with a high sensitivity of 0.097 ± 0.001 nA/μM and one-week storage stability. The biosensor also showed a rapid steady state response to L-glutamate within 2 s, with a limit of detection of 0.044 μM. The biosensor was used successfully to detect stimulated glutamate in the subthalamic nucleus in brain slices and in vivo. Thus, this biosensor is appropriate for future neuroscience applications.
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paper_title: Microelectrode Arrays of Diamond-Insulated Graphitic Channels for Real-Time Detection of Exocytotic Events from Cultured Chromaffin Cells and Slices of Adrenal Glands

paper_content:

A microstructured graphitic 4 × 4 multielectrode array was embedded in a single-crystal diamond substrate (4 × 4 μG-SCD MEA) for real-time monitoring of exocytotic events from cultured chromaffin cells and adrenal slices. The current approach relies on the development of a parallel ion beam lithographic technique, which assures the time-effective fabrication of extended arrays with reproducible electrode dimensions. The reported device is suitable for performing amperometric and voltammetric recordings with high sensitivity and temporal resolution, by simultaneously acquiring data from 16 rectangularly shaped microelectrodes (20 × 3.5 μm(2)) separated by 200 μm gaps. Taking advantage of the array geometry we addressed the following specific issues: (i) detect both the spontaneous and KCl-evoked secretion simultaneously from several chromaffin cells directly cultured on the device surface, (ii) resolve the waveform of different subsets of exocytotic events, and (iii) monitoring quantal secretory events from thin slices of the adrenal gland. The frequency of spontaneous release was low (0.12 and 0.3 Hz, respectively, for adrenal slices and cultured cells) and increased up to 0.9 Hz after stimulation with 30 mM KCl in cultured cells. The spike amplitude as well as rise and decay time were comparable with those measured by carbon fiber microelectrodes and allowed to identify three different subsets of secretory events associated with "full fusion" events, "kiss-and-run" and "kiss-and-stay" exocytosis, confirming that the device has adequate sensitivity and time resolution for real-time recordings. The device offers the significant advantage of shortening the time to collect data by allowing simultaneous recordings from cell populations either in primary cell cultures or in intact tissues.
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paper_title: Simultaneous measurements of ascorbate and glutamate in vivo in the rat brain using carbon fiber nanocomposite sensors and microbiosensor arrays

paper_content:

Nanocomposite sensors consisting of carbon fiber microelectrodes modified with Nafion® and carbon nanotubes, and ceramic-based microelectrode biosensor arrays were used to measure ascorbate and glutamate in the brain with high spatial, temporal and chemical resolution. Nanocomposite sensors displayed electrocatalytic properties towards ascorbate oxidation, translated into a negative shift from +0.20V to -0.05V vs. Ag/AgCl, as well as a significant increase (10-fold) of electroactive surface area. The estimated average basal concentration of ascorbate in vivo in the CA1, CA3 and dentate gyrus (DG) sub regions of the hippocampus were 276±60μM (n=10), 183±30μM (n=10) and 133±42μM (n=10), respectively. The glutamate microbiosensor arrays showed a high sensitivity of 5.3±0.8pAμM-1 (n=18), and LOD of 204±32nM (n=10), and t50% response time of 0.9±0.02s (n=6) and high selectivity against major interferents. The simultaneous and real-time measurements of glutamate and ascorbate in the hippocampus of anesthetized rats following local stimulus with KCl or glutamate revealed a dynamic interaction between the two neurochemicals.
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paper_title: Recent development in amperometric measurements of vesicular exocytosis

paper_content:

Abstract Vesicular exocytosis is a ubiquitous bio-process involved in plenty of normal and pathologic events in living cells and has received increasing research attention. After decades of progress, amperometry has been demonstrated to be one of the most powerful techniques to monitor the exocytotic release in real time because of its remarkable advantages such as facility to implement, high sensitivity and sub-millisecond temporal resolution. In this review, we provide an overview of recent advances in electrochemical courses related to exocytotic secretions. The principle for amperometric characterization of quantal exocytosis is briefly introduced. Development of mircrofabricated architectures for amperometric detection and their contributions are summarized. An intimate coupling of amperometry and fluorescence imaging for in-situ exocytosis tracking are highlighted.
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paper_title: An improved microbore UHPLC method with electrochemical detection for the simultaneous determination of low monoamine levels in in vivo brain microdialysis samples.

paper_content:

The simultaneous determination of the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in in vivo microdialysis samples remains challenging because of the low extracellular neurotransmitter levels in different brain regions, specific sample characteristics, and the quest for high temporal resolution and a multi-target strategy in neuropharmacological research. A fast and sensitive microbore (1.0 mm i.d. column) UHPLC method coupled to electrochemical detection (ECD) is developed by means of design of experiments with the emphasis on sufficient retention of NA within an acceptable total analysis time. Indeed, NA is the earliest eluting compound and often interferes with the broad solvent front originating from the sample matrix. The sensitive UHPLC-ECD assay (LLOQ of 100 pM for NA and 150 pM for DA and 5-HT) with an analysis time of 8 min for standard solutions and 20 min for in vivo microdialysis samples originating from rat hippocampus, prefrontal cortex and striatum, is validated applying accuracy profiles. The combination of in vivo microdialysis and microbore UHPLC-ECD has shown to be particularly suitable for future contributions to neuropharmacological research on the monoaminergic system.
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paper_title: Printed Carbon Microelectrodes for Electrochemical Detection of Single Vesicle Release from PC12 Cells

paper_content:

We present a disposable system for recording neurotransmitter release from individual cells in vitro. A simple yet reliable microelectrode fabrication process is introduced using screen-printed carbon paste. It allows rapid fabrication of devices at low costs without standard clean-room technology. We demonstrate functionality of the system by real-time observation of vesicle release from single PC12 (rat pheochromocytoma) cells. The cells are cultured directly on the chip and can be used for immediate or long-term in vitro experiments. Thus, our approach may serve as a platform for pharmacological cell culture studies.
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paper_title: Broccoli-shaped Biosensor Hierarchy for Electrochemical Screening of Noradrenaline in Living Cells

paper_content:

Abstract Monitoring and determination of ultra-trace concentrations of monoamine neurotransmitter such as noradrenaline (NA) in living cells with simple, sensitive and selective assays are significantly interesting. We design NA-electrode sensing system based on C-, N-doped NiO broccoli-like hierarchy (CNNB). The spherical broccoli-head umbrella architectures associated with nano-tubular arrangements enabled to tailor NA biosensor design. The homogenous doping and anisotropic dispersion of CN nanospheres along the entire NB head nanotubes lead to creating of abundant electroactive sites in the interior tubular vessels and outer surfaces for ultrasensitive detection of NA in living cells such as PC12. The CNNB biosensor electrodes showed efficient electrocatalytic activity, enhanced kinetics for electrooxidation of NA, and fast electron-transfer between electrode–electrolyte interface surfaces, enabling synergistic enhancement in sensitivity, and selectivity at a low-detectable concentration of ∼ 6 nM and reproducibility of broccoli-shaped NA-electrodes. The integrated CNNB biosensor electrodes showed evidence of monitoring and screening of NA released from PC12 cells under K + ion-extracellular stimulation process. The unique features of CNNB in terms of NA-selectivity among multi-competitive components, long-term stability during the detection of NA may open their practical, in-vitro application for extracellular monoamine neurotransmitters detection in living cells.
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paper_title: An amperometric glutamate biosensor for monitoring glutamate release from brain nerve terminals and in blood plasma

paper_content:

An excess of the excitatory neurotransmitter, glutamate, in the synaptic cleft during hypoxia/ischemia provokes development of neurotoxicity and originates from the reversal of Na+-dependent glutamate transporters located in the plasma membrane of presynaptic brain nerve terminals. Here, we have optimized an electrochemical glutamate biosensor using glutamate oxidase and developed a biosensor-based methodological approach for analysis of rates of tonic, exocytotic and transporter-mediated glutamate release from isolated rat brain nerve terminals (synaptosomes). Changes in the extracellular glutamate concentrations from 11.5 ± 0.9 to 11.7 ± 0.9 μΜ for 6 min reflected a low tonic release of endogenous glutamate from nerve terminals. Depolarization-induced exocytotic release of endogenous glutamate was equal to 7.5 ± 1.0 μΜ and transporter reversal was 8.0 ± 1.0 μΜ for 6 min. The biosensor data correlated well with the results obtained using radiolabelled L-[14C]glutamate, spectrofluorimetric glutamate dehydrogenase and amino acid analyzer assays. The blood plasma glutamate concentration was also tested, and reliability of the biosensor measurements was confirmed by glutamate dehydrogenase assay. Therefore, the biosensor-based approach for accurate monitoring rates of tonic, exocytotic and transporter-mediated release of glutamate in nerve terminals was developed and its adequacy was confirmed by independent analytical methods. The biosensor measurements provided precise data on changes in the concentrations of endogenous glutamate in nerve terminals in response to stimulation. We consider that the glutamate biosensor-based approach can be applied in clinics for neuromonitoring glutamate-related parameters in brain samples, liquids and blood plasma in stroke, brain trauma, therapeutic hypothermia treatment, etc., and also in laboratory work to record glutamate release and uptake kinetics in nerve terminals.
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paper_title: In situ detection of neurotransmitters and epileptiform electrophysiology activity in awake mice brains using a nanocomposites modified microelectrode array

paper_content:

Abstract A novel nanocomposites modified microelectrode array (MEA) was designed and fabricated for in situ detection of neurotransmitters (glutamate and dopamine) and electrophysiology activity. The MEAs were implanted into the hippocampus of four epileptic mice to detect the neuron activity along with their behaviours. Six spontaneous seizures were recorded, with each seizure having 5 periods. From the normal to the pre-seizure period, both the concentrations of neurotransmitters and the intensities of electrophysiology activities increased by 20%–70%. During the seizure period, the glutamate level dramatically increased to approximately 10 times its normal, while the dopamine level sharply decreased to approximately one third of the normal; the spike firing rate and the power of the local field potential significantly increased more than three-fold. During the inhibitory period, neurotransmitters and electrophysiology activities were significantly inhibited, and then they gradually returned to normal. These results revealed that seizures were highly correlated with glutamate, dopamine and electrophysiology activity and abnormalities in the neuron activity appeared earlier than any abnormal behaviour. Moreover, synchronized changes of these multiple signals in the pre-seizure period could be used to predict seizures. This novel MEA provides an effective technology and a new perspective for understanding the epileptic mechanism.
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paper_title: Electroanalysis of neurotransmitters via 3D gold nanoparticles and a graphene composite coupled with a microdialysis device

paper_content:

Abstract We developed a novel biosensor, which used the uniform graphene oxide (GO) to afford gold nanoparticles (GNPs). The advantages of this biosensor are the better sensitivities not only of GO but also the GNPs fabricated on it for neurotransmitters, especially the lower cost in biosensor modification. The modified composite was characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), energy dispersive spectroscopy (EDS) and electrochemical methods. The determination conditions were optimized and the peak currents of DA and 5‑HT were linear, with the concentrations in the range of 9.0 × 10−7 to 7.0 × 10−5 M for DA, and 6.0 × 10−7 to 4.0 × 10−5 M for 5‑HT. The detection limits were 7.0 × 10−9 M for 5‑HT and 5.6 × 10−8 M for DA. A micro-capacity electrolytic cell was designed using the modified biosensor to connect to the microdialysis device and it was successfully applied to determine the concentrations of DA and 5‑HT in the samples, with a spiked recovery of 82.0–118%.
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paper_title: Polyethylenimine Carbon Nanotube Fiber Electrodes for Enhanced Detection of Neurotransmitters

paper_content:

Carbon nanotube (CNT)-based microelectrodes have been investigated as alternatives to carbon-fiber microelectrodes for the detection of neurotransmitters because they are sensitive, exhibit fast electron transfer kinetics, and are more resistant to surface fouling. Wet spinning CNTs into fibers using a coagulating polymer produces a thin, uniform fiber that can be fabricated into an electrode. CNT fibers formed in poly(vinyl alcohol) (PVA) have been used as microelectrodes to detect dopamine, serotonin, and hydrogen peroxide. In this study, we characterize microelectrodes with CNT fibers made in polyethylenimine (PEI), which have much higher conductivity than PVA-CNT fibers. PEI-CNT fibers have lower overpotentials and higher sensitivities than PVA-CNT fiber microelectrodes, with a limit of detection of 5 nM for dopamine. The currents for dopamine were adsorption controlled at PEI-CNT fiber microelectrodes, independent of scan repetition frequency, and stable for over 10 h. PEI-CNT fiber microelectrodes w...
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paper_title: Laser Treated Carbon Nanotube Yarn Microelectrodes for Rapid and Sensitive Detection of Dopamine in Vivo

paper_content:

Carbon nanotube yarn microelectrodes (CNTYMEs) exhibit rapid and selective detection of dopamine with fast-scan cyclic voltammetry (FSCV); however, the sensitivity limits their application in vivo. In this study, we introduce laser treatment as a simple, reliable, and efficient approach to improve the sensitivity of CNTYMEs by threefold while maintaining high temporal resolution. The effect of laser treatment on the microelectrode surface was characterized by scanning electron microscopy, Raman spectroscopy, energy dispersion spectroscopy, and laser scanning confocal microscopy. Laser treatment increases the surface area and oxygen containing functional groups on the surface, which provides more adsorption sites for dopamine than at unmodified CNTYMEs. Moreover, similar to unmodified CNTYMEs, the dopamine signal at laser treated CNTYMEs is not dependent on scan repetition frequency, unlike the current at carbon fiber microelectrodes (CFMEs) which decreases with increasing scan repetition frequency. This f...
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paper_title: Ultrasensitive in-vitro monitoring of monoamine neurotransmitters from dopaminergic cells

paper_content:

Abstract The design of biosensing assay of monoamine neurotransmitters (MANTs) such as epinephrine (Ep), norepinephrine (NE), and dopamine (DA), as well as the monitoring of these MANTs released from dopaminergic cells, are of particular interest. Electrochemical sensors based on the novel construction of nickel oxides (NiO) were fabricated and employed for electrochemical screening of MANTs. A novel NiO-lacy flower-like (NLF) geometrical structure with semi-spherical head surfaces connected with a trunk as an arm was achieved. The designed semi-spherical head associated with abundant and the well-dispersed tubular branches with needle-like open ends might lead to the creation of vascular vessels for facile diffusion and suitable accommodation of the released MANTs throughout active and wide-surface-area coverage, multi-diffusive pores, and caves with connective open macro-/meso-windows along the entire top-view nanoneedles of lacy flower head and trunk. These electrode surfaces possess high-index catalytic site facets associated with the formation of ridges/defects on {110}-top-cover surface dominants for strong binding, fast response, and signaling of MANTs. The NLF- modified electrode enabled high sensitivity for MANTs and a low limit of detection of 6 nM. Ultrasensitive in-vitro monitoring of DA released from dopaminergic cells (such as PC12) was realized. The NLF electrode was used to detect MANTs from its sources (PC12), and it could be used for clinical diagnosis.
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paper_title: Tracking Tonic Dopamine Levels in vivo using Multiple Cyclic Square Wave Voltammetry

paper_content:

Abstract For over two decades, fast-scan cyclic voltammetry (FSCV) has served as a reliable analytical method for monitoring dopamine release in near real-time in vivo. However, contemporary FSCV techniques have been limited to measure﻿ only rapid (on the order of seconds, i.e. phasic) changes in dopamine release evoked by either electrical stimulation or elicited by presentation of behaviorally salient stimuli, and not slower changes in the tonic extracellular levels of dopamine (i.e. basal concentrations). This is because FSCV is inherently a differential method that requires subtraction of prestimulation tonic levels of dopamine to measure phasic changes relative to a zeroed baseline. Here, we describe the development and application of a novel voltammetric technique, multiple cyclic square wave voltammetry (M-CSWV), for analytical quantification of tonic dopamine concentrations in vivo with relatively high temporal resolution (10 s). M-CSWV enriches the electrochemical information by generating two dimensional voltammograms which enable high sensitivity (limit of detection, 0.17 nM) and selectivity against ascorbic acid, and 3,4-dihydroxyphenylacetic acid (DOPAC), including changes in pH. Using M-CSWV, a tonic dopamine concentration of 120 ± 18 nM (n = 7 rats, ± SEM) was determined in the striatum of urethane anethetized rats. Pharmacological treatments to elevate dopamine by selectively inhibiting dopamine reuptake and to reduce DOPAC by inhibition of monoamine oxidase supported the selective detection of dopamine in vivo. Overall, M-CSWV offers a novel voltammetric technique to quantify levels and monitor changes in tonic dopamine concentrations in the brain to further our understanding of the role of dopamine in normal behavior and neuropsychiatric disorders.
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paper_title: Carbon-Ring Microelectrode Arrays for Electrochemical Imaging of Single Cell Exocytosis: Fabrication and Characterization

paper_content:

Fabrication of carbon microelectrode arrays, with up to 15 electrodes in total tips as small as 10–50 μm, is presented. The support structures of microelectrodes were obtained by pulling multiple quartz capillaries together to form hollow capillary arrays before carbon deposition. Carbon ring microelectrodes were deposited by pyrolysis of acetylene in the lumen of these quartz capillary arrays. Each carbon deposited array tip was filled with epoxy, followed by beveling of the tip of the array to form a deposited carbon-ring microelectrode array (CRMA). Both the number of the microelectrodes in the array and the tip size are independently tunable. These CRMAs have been characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, and electrogenerated chemiluminescence. Additionally, the electrochemical properties were investigated with steady-state voltammetry. In order to demonstrate the utility of these fabricated microelectrodes in neurochemistry, CRMAs containing eight microri...
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paper_title: Recent trends in analytical approaches for detecting neurotransmitters in Alzheimer's disease

paper_content:

Abstract Alzheimer's disease is a progressive neurodegenerative disease that involves loss of memory, thinking, and reasoning and several behavioral characteristics. Alzheimer's disease affects an individual in a drastic manner by exhibiting its impact on the individual's daily routine. A completely accurate diagnosis can be achieved only after the death of a patient by observing the plaques and tangles in the brain. Hence, it is important that researchers develop robust diagnostic tools for detecting Alzheimer's disease. Neurotransmitters are suitable biomarkers for various neurological disorders, such as Parkinson's disease, Alzheimer's disease, and depression. In recent years, various analytical techniques for the detection of neurotransmitters have emerged. In this review article, we discuss the recent trends of such techniques and their limitations in the detection of various biomarkers involved in Alzheimer's disease. Furthermore, we investigate the recent progress in nanotechnology-based methods and future perspectives for the detection of neurotransmitters.
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paper_title: An electrochemical biosensor based on double molecular recognition for selective monitoring of cerebral dopamine dynamics at 4 min interval

paper_content:

Abstract Dopamine (DA) monitoring with high selectivity and sensitivity in the cerebrally extracellular fluid is of high value for evaluating the role of DA in the physiological and pathological processes. Especially because neurotransmission involved in rapid events, lowering the detection interval in order to gain more insight into DA dynamics inserts great challenge into the DA analytical method. In this work, a facile electrochemical biosensor for sensing DA with high sensitivity was developed here. Double molecular recognition based on boronic acid-diol and N-hydroxysuccinimide ester-amine endows the new biosensor favourable selectivity for cerebral DA detection. More importantly, microdialysate volume as low as 7 μL was requisite for the DA analysis without suffering from a sensitivity loss, thus monitoring DA concentration in brain microdialysate at 4 min interval was successfully achieved. Subsequently, the present biosensor was successfully employed for monitoring of cerebral DA transients evoked by high K+ and nomifensine.
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paper_title: FDG-PET imaging in mild traumatic brain injury: a critical review

paper_content:

Traumatic brain injury (TBI) affects an estimated 1.7 million people in the United States and is a contributing factor to one third of all injury related deaths annually. According to the CDC, approximately 75% of all reported TBIs are concussions or considered mild in form, although the number of unreported mild TBIs and patients not seeking medical attention is unknown. Currently, classification of mild TBI (mTBI) or concussion is a clinical assessment since diagnostic imaging is typically inconclusive due to subtle, obscure, or absent changes in anatomical or physiological parameters measured using standard magnetic resonance (MR) or computed tomography (CT) imaging protocols. Molecular imaging techniques that examine functional processes within the brain, such as measurement of glucose uptake and metabolism using [18F]fluorodeoxyglucose and positron emission tomography (FDG-PET), have the ability to detect changes after mild TBI. Recent technological improvements in the resolution of PET systems, the integration of PET with MRI, and the availability of normal healthy human databases and commercial image analysis software contribute to the growing use of molecular imaging in basic science research and advances in clinical imaging. This review will discuss the technological considerations and limitations of FDG-PET, including differentiation between glucose uptake and glucose metabolism and the significance of these measurements. In addition, the current state of FDG-PET imaging in assessing mild TBI in clinical and preclinical research will be considered. Finally, this review will provide insight into potential critical data elements and recommended standardization to improve the application of FDG-PET to mild TBI research and clinical practice.
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paper_title: Electrochemical sensor and biosensor platforms based on advanced nanomaterials for biological and biomedical applications.

paper_content:

Introduction of novel functional nanomaterials and analytical technologies signify a foremost possibility for the advance of electrochemical sensor and biosensor platforms/devices for a broad series of applications including biological, biomedical, biotechnological, clinical and medical diagnostics, environmental and health monitoring, and food industries. The design of sensitive and selective electrochemical biological sensor platforms are accomplished conceivably by offering new surface modifications, microfabrication techniques, and diverse nanomaterials with unique properties for in vivo and in vitro medical analysis via relating a sensibly planned electrode/solution interface. The advantageous attributes such as low-cost, miniaturization, energy efficient, easy fabrication, online monitoring, and the simultaneous sensing capability are the driving force towards continued growth of electrochemical biosensing platforms, which have fascinated the interdisciplinary research arenas spanning chemistry, material science, biological science, and medical industries. The electrochemical biosensor platforms have potential applications in the early-stage detection and diagnosis of disease as stout and tunable diagnostic and therapeutic systems. The key aim of this review is to emphasize the newest development in the design of sensing and biosensing platforms based on functional nanomaterials for biological and biomedical applications. High sensitivity and selectivity, fast response, and excellent durability in biological media are all critical aspects which will also be wisely addressed. Potential applications of electrochemical sensor and biosensor platforms based on advanced functional nanomaterials for neuroscience diagnostics, clinical, point-of-care diagnostics and medical industries are also concisely presented.
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paper_title: A microelectrochemical biosensor for real-time in vivo monitoring of brain extracellular choline

paper_content:

A first generation Pt-based polymer enzyme composite biosensor developed for real-time neurochemical monitoring was characterised in vivo for sensitive and selective detection of choline. Confirmation that the sensor responds to changes in extracellular choline was achieved using local perfusion of choline which resulted in an increase in current, and the acetylcholinesterase inhibitor neostigmine which produced a decrease. Interference by electroactive species was tested using systemic administration of sodium ascorbate which produced a rapid increase in extracellular levels before gradually returning towards baseline over several hours. There was no overall change in the response of the biosensor during the same period of monitoring. Oxygen interference was examined using pharmacological agents known to change tissue oxygenation. Chloral hydrate produced an immediate increase in O2 before gradually returning to baseline levels over 3 h. The biosensor signal displayed an initial brief decrease before increasing to a maximum after 1 h and returning to baseline within 2 h. L-NAME caused a decrease in O2 before returning to baseline levels after ca. 1.5 h. In contrast, the biosensor current increased over the same time period before slowly returning to baseline levels over several hours. Such differences in time course and direction suggest that changes in tissue O2 levels do not affect the ability of the sensor to monitor choline reliably. Although it was found to rapidly respond to behavioural activation, examination of baseline in vivo data suggests a stable viable signal for at least 14 days after implantation. Using in vitro calibration data the basal extracellular concentration of choline was estimated to be 6.3 μM.
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paper_title: Development of a microelectrochemical biosensor for the real-time detection of choline

paper_content:

Abstract Here we describe the development of a first generation biosensor for the detection of brain extracellular choline, investigating important considerations for in-vivo monitoring such as sensor sensitivity, O 2 interference and selectivity. Extensive optimisation of choline biosensor designs resulted in a biosensor with excellent sensitivity towards choline (0.54 ± 0.03 nA/μM). Oxygen interference studies demonstrate a 1% reduction in current at 50 μM O 2 when compared to atmospheric O 2 levels (200 μM), indicating that the sensor can be used for reliable choline monitoring, free from changes in current associated with physiological O 2 fluctuations. A negligible sensitivity of 0.0021 ± 0.0002 nA/μM n = 8 was achieved utilising poly-phenylenediamine (PPD) as a permselective membrane for interference rejection of ascorbic acid (AA), the most physiologically important endogenous electroactive species present in the brain. The optimised biosensor when implanted into the striatum of a freely moving rat successfully detected local perfusions of choline demonstrating the sensors ability to detect choline in-vivo.
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Title: Latest Trends in Electrochemical Sensors for Neurotransmitters: A Review

Section 1: Introduction
Description 1: Introduce the importance of neurotransmitters, their discovery, classification, physiological roles, and the need for their quantitative detection.

Section 2: Electrochemical Sensors
Description 2: Provide an overview of electrochemical sensors, their advantages over other transduction systems, and the various materials and modifications used to enhance sensor performance.

Section 3: Non-Enzymatic Electrochemical Sensors
Description 3: Discuss the different types of non-enzymatic electrochemical sensors, highlighting their use in the direct detection of electroactive neurotransmitters.

Section 4: Amino Acid Neurotransmitters
Description 4: Detail the electrochemical detection approaches and sensor developments specifically for amino acid neurotransmitters like glutamate.

Section 5: Biogenic Amines Neurotransmitters
Description 5: Describe the latest sensor technology for detecting biogenic amines like dopamine, epinephrine, norepinephrine, and serotonin.

Section 6: Enzyme Sensors
Description 6: Explain the role of enzyme-based sensors in neurotransmitter detection, including various immobilization strategies and their advantages.

Section 7: Biosensors for In Vitro, In Vivo and Ex Vivo Measurements
Description 7: Cover the use of biosensors for monitoring neurotransmitter levels in various experimental conditions, highlighting recent advancements and applications.

Section 8: Conclusions
Description 8: Summarize the key findings of the review, the importance of electrochemical biosensors for clinical diagnostics, and future directions in neurotransmitter sensor development.