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The catalytic properties of metallophthalocyanine (MPc) complexes have long been applied to electrochemical sensing of nitric oxide (NO) to amplify sensitivity and reduce the substantial overpotential required for NO oxidation. The latter point has significant ramifications for in situ amperometric detection, as large working potentials oxidize biological interferents (e.g., nitrite, l -ascorbate, and carbon monoxide). Herein, we sought to isolate and quantify, for the first time, the selectivity benefits of MPc modification of glassy carbon electrodes. A series of the most catalytically active MPc complexes towards NO, including Fe(II)Pc, Co(II)Pc, Ni(II)Pc, and Zn(II)Pc, was selected and probed for NO sensing ability under both differential pulse voltammetry (DPV) and constant potential amperometry (CPA). Data from DPV measurements provided information with respect to MPc signal sensitivity amplification (∼1.5×) and peak shifting (100–200 mV). Iron-Pc exerted the most specific catalytic activity towards NO over nitrite. Catalyst-enabled reduction of the working potential under CPA was found to improve selectivity for NO over high potential interferents, regardless of MPc. However, impaired selectivity against low potential interferents was also noted. [ABSTRACT FROM AUTHOR]

An electrochemical method capable of direct, real-time detection of hydrogen sulfide was developed using triple pulse amperometry (TPA) to mitigate sulfur poisoning and its related passivation of the working electrode surface. Through repeated cycles of discrete potential pulses, the electrooxidation of surface-adsorbed elemental sulfur to water-soluble sulfate ions was exploited to regenerate the glassy carbon electrode surface and maintain consistent sensor performance. Amperometric measurements and X-ray photoelectron spectroscopy surface analysis demonstrated that the TPA sensors provided enhanced analytical performance via decreased sulfur accumulation relative to low-potential (≤+0.7 V) constant potential amperometry. Sensors operated under optimized TPA parameters retained high sensitivity (57.4 ± 13.0 nA/µM), a wide linear dynamic range (150 nM-15 µM), fast response times (<10 s), and a submicromolar detection limit (<100 nM) upon consecutive calibration cycles. The sensitivity and response time achieved were comparable to or better than current electrochemical sensors. Moreover, the simplicity of the method eliminates the need for external redox mediators or semipermeable membranes. [ABSTRACT FROM AUTHOR]

A 530 nm light emitting diode was coupled to a microfluidic sensor tofacilitate photolysis of nitrosothiols (i.e., S-nitrosoglutathione, S-nitrosocysteine, and S-nitrosoalbumin) and amperometric detection of the resulting nitric oxide (NO). This configuration allowed for maximum sensitivity and versatility, while limiting potential interference from nitrate decomposition caused by ultraviolet light. Compared to similar measurements of total S-nitrosothiol content in bulk solution, use of the microfluidic platform permitted significantly enhanced analytical performance in both phosphate-buffered saline and plasma (6-20× improvement in sensitivity depending on nitrosothiol type). Additionally, the ability to reduce sample volumes from milliliters to microliters provides increased clinical utility. To demonstrate its potential for biological analysis, this device was used to measure basal nitrosothiol levels from the vasculature of a healthy porcine model. [ABSTRACT FROM AUTHOR]

The phytotoxicity of silica nanoparticles (SiNPs) was evaluated as a function of particle size (14, 50, and 200 nm), concentration (250 and 1000 mg L-1), and surface composition toward Arabidopsis thaliana plants grown hydroponically for 3 and 6 weeks. Reduced development and chlorosis were observed for plants exposed to highly negative SiNPs (-20.3 and -31.9 mV for the 50 and 200 nm SiNPs, respectively) regardless of particle concentration when not controlling pH of the hydroponic medium, which resulted in increased alkalinity (pH 8). Particles were no longer toxic to the plants at either concentration upon calcination or removal of surface silanols from the SiNP surface, or adjusting the pH of the growth medium to pH 5.8. The phytotoxic effects observed for the negatively charged 50 and 200 nm SiNPs were attributed to pH effects and the adsorption of macro- and micro-nutrients to the silica surface. Size-dependent uptake of the nanoparticles by the plants was confirmed using transmission electron microscopy (TEM) and inductively coupled plasma-optical emission spectroscopy (ICP-OES) with plant roots containing 32.0, 1.85, and 7.00 × 10-3 mg Si·kg tissue-1/nm3 (normalized for SiNP volume) for the 14, 50, and 200 nm SiNPs respectively, after 6 weeks exposure at 1000 ppm (pH 5.8). This study demonstrates that the silica scaffolds are not phytotoxic up to 1000 ppm despite significant uptake of the SiNPs (14, 50, and 200 nm) into the root system of A. thaliana. [ABSTRACT FROM AUTHOR]

Abstract: The ability of nitric oxide (NO)-releasing xerogels to reduce adhesion of Pseudomonas aeruginosa under flowing conditions was evaluated using a parallel plate flow chamber. At a controlled bacterial suspension flow rate of 0.2mL/min, the NO-releasing xerogels reduced bacterial adhesion in a flux-dependent fashion, with an NO flux of ∼21pmolcm−2 s−1 reducing P. aeruginosa adhesion by ∼65% compared to controls. Fluorescent viability staining indicated that bacteria adhered to NO-releasing xerogels were killed within 7h. Quantitative cell-plating viability studies showed that the extent of bactericidal activity was dependent on the total amount of NO released, with 750nmolcm−2 killing >90% more adhered bacteria than xerogels releasing 25nmolcm−2. Thus, NO-releasing xerogels were shown to both inhibit P. aeruginosa adhesion and kill adhered bacteria cells, two important steps toward designing anti-infective biomaterial coatings. [Copyright &y& Elsevier]

Abstract: Nitric oxide (NO)-releasing xerogel membranes were prepared as coatings for an electrochemical glucose biosensor to allow for enhanced biocompatibility while maintaining adequate response times and sensitivity. Formation of the NO-donor species was found to drastically decrease the permeability of the aminosilane-based xerogels to both hydrogen peroxide and glucose. The addition of poly(vinylpyrrolidone) (PVP) polymer enhanced the membrane permeability even after exposure to high pressures of NO (necessary for NO-donor synthesis). The analytical response and NO release of PVP-doped NO-releasing xerogels as glucose sensor membranes were further investigated and found to be enhanced via polymer doping. Doping of the polymer into the xerogel did not compromise the stability of the xerogel as evaluated by silicon leaching studies. Despite the addition of PVP, the NO-releasing xerogels maintained reduced bacterial adhesion characteristics analogous to previous reports for NO-releasing xerogels. [Copyright &y& Elsevier]

The preparation and characterization of nitric oxide (NO)-releasing dendrimer conjugates are reported. Generation 3 and 5 polypropylenimine dendrimers (DAB-Am-16 and DAB-Am-64) were modified at the exterior to impart different amine functionalities. The ability to store NO on a dendritic scaffold using N-diazeniumdiolate NO donors was examined via the reaction of primary amine, secondary amine, and amide functionalities with high pressures of NO (5 atm). The secondary amine dendrimer conjugates exhibited a high storage capacity for NO (up to 5.6 μmol NO/mg), greatly increasing the ‘payload’ of released NO over existing macromolecular NO donors. The mechanism of diazeniumdiolate decomposition was proton initiated, generating NO spontaneously under physiological conditions (pH 7.4, 37 °C). The NO release durations (> 16 h) observed for the secondary amine dendrimers were significantly longer compared to small molecule alkyl secondary amine diazeniumdiolates, thus illustrating a dendritic effect on NO release kinetics. The multivalent exterior of dendrimers allows for the future combination of NO donors and other functionalities on a single molecular scaffold, enabling diverse utility as NO storage/delivery systems. [ABSTRACT FROM AUTHOR]

Abstract: The cytotoxicity of bare and PU-coated nitric oxide (NO)-releasing sol–gel derived materials (sol–gels) was investigated using L929 mouse fibroblasts in both direct and indirect contact models to differentiate between the biological impact of the sol–gel matrix and NO release. The flux of NO was varied up to 150pmolcm-2s-1 using N-(6-aminohexyl)-aminopropyltrimethoxysilane (balance iso-butyltrimethoxysilane) diazeniumdiolate (NO donor)-modified sol–gels. The addition of a polyurethane (PU) outer membrane greatly improved the stability of the sol–gel matrix without significantly suppressing the NO flux. Direct contact studies demonstrated a cytotoxic effect that was dependent on the aminosilane content of the sol–gel. The use of the thin PU overcoat eliminated this effect. A direct cytotoxicity dependence of NO release for L929 fibroblasts was discovered from indirect contact studies, where 24h exposure to NO fluxes in excess of 50pmolcm-2s-1 was cytotoxic. [Copyright &y& Elsevier]

A potentiometric sol-gel derived (xerogel) pH sensor based on covalently attached amine groups is described. The sensor consists of a Ag/AgCI electrode coated with a hybrid aminosilane/alkylsilane xerogel film. Various combinations of aminosilanes and alkylsilanes are evaluated for theft potentiomeiric response to pH. The optimal sensor design is composed of (aminoethylaminomethyl)- phenethyltrimethoxysilane and methyltrimethoxysilane. This sensorexhibisnear-Nerstianresponse(-55mV.decade-1), responds rapidly (≤3 s) to changes in pH, and has H+ selectivity coefficients (log KPotH+, j) of -13 and -11 for interfering j cations Na+ and K+, respectively. In vitro platelet adhesion tests indicate that the xerogel coatings are more blood compatible than conventional poly(vinyl chloride) and poly(urethane) ion-selective electrode coatings. [ABSTRACT FROM AUTHOR]

Examines the in vitro analytical performance of nitric oxide (NO)-releasing fluorescence-based oxygen sensing polymeric film prepared with silicone rubbers. Observation of nonlinear Stern-Volmer behavior for single-layer NO release oxygen sensors; Identical sensitivity and linearity toward oxygen.

Discusses the development of a nitric oxide (NO)-releasing amperometric oxygen sensor. Increased thromboresistivity of the sensor; Advantages of using gas permeable coatings formulated with cross-linked silicone rubber containing NO compounds; Reduction in thrombus formation on the surfaces of the sensor.

Presents information on a study which investigated the impact of air exposure on self-assembled monolayers' stability, which were formed from alkanethiols on antigens and Au surfaces. Details on the usage of surface Raman spectroscopy, electrochemistry and X-ray photoelectron; Exhibition of oxidized sulfur modes by Raman spectra after hour of air exposure; Methodology used to conduct the study; Results of the study.

The article focuses on an interactive analytical chemistry summer camp for middle school girls. The goal of this camp is to provide girls with a unique opportunity to experience analytical chemistry in a way that will spark their interest in how it is studied, its roles in modern scientific research, and the diversity of educational and career opportunities that science has to offer. The entirely female staff is composed of five Department of Chemistry graduate students and three undergraduate Department of Education teaching fellows. Preparation for the program begins several weeks prior to the camp with the graduate students helping the teaching fellows to complete each experiment. The summer camp program proves beneficial to participants at each level. The chemistry graduate student instructors have a unique opportunity to improve their ability to communicate with a more general audience about science and research. This program offers a memorable experience for middle school girls by coupling interactive analytical chemistry experiments with the opportunity to develop mentoring relationships with devoted female graduate students.

Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species. [ABSTRACT FROM AUTHOR]

• Delivery of nitric oxide by a chitosan donor allowed for higher in-solution concentrations of nitric oxide compared to gaseous delivery. • Gaseous delivery resulted in solution nitric oxide concentrations that were both medium- and volume-dependent. • Nitric oxide-releasing chitosan was a superior antibiofilm and mucolytic agent over nitric oxide gas. • Localized, in-solution delivery via nitric oxide-releasing chitosan allowed for greater bactericidal action. The combination of antibacterial and mucolytic actions makes nitric oxide (NO) an attractive dual-action cystic fibrosis (CF) therapeutic. The delivery of any therapeutic agent through pathological mucus is difficult, and the use of inhaled NO gas is inherently limited by toxicity concerns. Herein, we directly compare the ability of NO to eradicate infection and decrease mucus viscoelastic moduli as a function of delivery method (i.e., as a gas or water-soluble chitosan donor). To compare bactericidal action in tissue, an ex vivo porcine lung model was infected and treated with either gaseous NO or NO-releasing chitosan for 5 h. In vitro Pseudomonas aeruginosa biofilm viability was quantified after NO treatment. Human bronchial epithelial mucus and CF sputum were exposed to NO and their viscoelastic moduli measured with parallel plate macrorheology. Larger NO concentrations were achieved in solution when delivered by chitosan relative to gas exposure. The bactericidal action in tissue of the NO-releasing chitosan was greater compared to NO gas in the infected tissue model. Chitosan delivery also resulted in improved antibiofilm action and reduced biofilm viability (2-log) while gaseous delivery had no impact at an equivalent dose (~0.8 µmol/mL). At equivalent NO doses, mucus and sputum rheology were significantly reduced after treatment with NO-releasing chitosan with NO gas having no significant effect. Delivery of NO by chitosan allows for larger in-solution concentrations than achievable via direct gas with superior bactericidal and mucolytic action. [ABSTRACT FROM AUTHOR]

Abstract Continuous, in situ detection of hydrogen sulfide (H 2 S) in biological milieu is made possible with electrochemical methods, but direct amperometry is constrained by the generation of elemental sulfur as an oxidative byproduct. Deposition of a sulfur layer passivates the working electrode, reducing sensitivity and causing performance variability. Herein, we report on the use of a surface preconditioning procedure to deposit elemental sulfur on a glassy carbon electrode prior to measurement and evaluate performance with common analytical metrics. The lack of traditional anti-poisoning techniques (e.g. redox mediators, cleaning pulses) also allowed for facile surface modification with electropolymerized films. For the first time, a series of electropolymerized films were characterized for their H 2 S permselective behavior against common biological interferents. Highly selective, film-modified electrodes were then evaluated for their anti-biofouling ability in simulated wound fluid. The final optimized electrode was capable of measuring H 2 S with a low detection limit (i.e., <100 nM) and ∼80% of its initial sensitivity in proteinaceous media. Graphical abstract Image 1 Highlights • Amperometric measurement of hydrogen sulfide (H 2 S) is challenging due to electrode poisoning with solid sulfur byproduct. • Concomitant electrode passivation reduces H 2 S sensitivity and results in performance variability with use. • Surface conditioning procedure on a glassy carbon electrode (GCE) evades passivation-related performance variability. • Use of electropolymerized film improves electrode's selectively for H 2 S and performance in biological media. [ABSTRACT FROM AUTHOR]

Examines the release of nitric oxide in sol-gel biomaterials. Synthesis of sol-gel materials; Reduction in platelet adhesion; Surface localized release of nitric oxide.

A series of injectable polysaccharide hydrogels are prepared with oxidized dextran and diethylenetriamine‐modified carboxymethylcellulose (CMC) or hyaluronic acid (HA). Rheological evaluation reveals that CMC‐based hydrogels achieve storage moduli >1 kPa when prepared from 5 wt% solutions, while storage moduli >100 Pa are achievable from solutions with concentrations as low as 2 wt%. HA‐based hydrogels demonstrate smaller storage moduli but have swelling ratios more than four‐fold that of CMC systems at equal concentrations. The incorporation of N‐diazeniumdiolate nitric oxide (NO) donors into the hydrogels results in reduced hydrogel storage moduli as a function of NO donor concentration. The impact of the hydrogel architecture on NO‐release kinetics proves dependent on the identity of the NO donor. Hydrogel degradation over 14 d indicates that HA‐based hydrogels degrade more rapidly than CMC hydrogels and that the addition of NO to the hydrogels increases the rate at which they degrade. In vitro cytotoxicity of hydrogel extracts is minimal, with toxicity observed only at high NO‐donor concentrations for select cell lines. The diverse properties, versatility, and nontoxic characteristics of these injectable hydrogels should facilitate local delivery of nitric oxide for a range of biomedical applications. [ABSTRACT FROM AUTHOR]

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• Klebsiella pneumoniae can cause highly resistant infections, including biofilms. • Classical or hypervirulent strains possess different capsule properties. • Nitric oxide exhibits broad-spectrum antibacterial activity and biofilm dispersal. • K. pneumoniae did not develop resistance against nitric oxide. • Nitric oxide reduced capsule mucoviscosity and dispersed biofilms of K. pneumoniae. Klebsiella pneumoniae is considered to be a critical public health threat due to its ability to cause fatal, multi-drug-resistant infections in the bloodstream and key organs. The polysaccharide-based capsule layer that shields K. pneumoniae from clearance via innate immunity is a prominent virulence factor. K. pneumoniae also forms biofilms on biotic and abiotic surfaces. These biofilms significantly reduce penetration by, and antibacterial activity from, traditional antibiotics. Nitric oxide (NO), an endogenous molecule involved in the innate immune system, is equally effective at eradicating bacteria but without engendering resistance. This study investigated the effects of NO-releasing small molecules capable of diverse release kinetics on the capsule and biofilm formation characteristics of multiple K. pneumoniae strains. The use of NO donors with moderate and extended NO-release properties (i.e., half-life >1.8 h) inhibited bacterial growth. Additionally, treatment with NO decreased capsule mucoviscosity in K. pneumoniae strains that normally exhibit hypermucoviscosity. The NO donors were also effective against K. pneumoniae biofilms at the same minimum biocidal concentrations that eliminated planktonic bacteria, while meropenem showed little antibacterial action in the same experiments. These results represent the first account of exogenous NO affecting biomarkers involved in K. pneumoniae infections, and may therefore inform future development of NO-based therapeutics for treating such infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Implantable glucose biosensors provide real-time information about blood glucose fluctuations, but their utility and accuracy are time-limited due to the foreign body response (FBR) following their insertion beneath the skin. The slow release of nitric oxide (NO), a gasotransmitter with inflammation regulatory properties, from a sensor surface has been shown to dramatically improve sensors' analytical biocompatibility by reducing the overall FBR response. Indeed, work in a porcine model suggests that as long as the implants (sensors) continue to release NO, even at low levels, the inflammatory cell infiltration and resulting collagen density are lessened. While these studies strongly support the benefits of NO release in mitigating the FBR, the mechanisms through which exogenous NO acts on the surrounding tissue, especially under the condition of hyperglycemia, remain vague. Such knowledge would inform strategies to refine appropriate NO dosage and release kinetics for optimal therapeutic activity. In this study, we evaluated mediator, immune cell, and mRNA expression profiles in the local tissue microenvironment surrounding implanted sensors as a function of NO release, diabetes, and implantation duration. A custom porcine wound healing-centric multiplex gene array was developed for nanoString barcoding analysis. Tissues adjacent to sensors with sustained NO release abrogated the implant-induced acute and chronic FBR through modulation of the tissue-specific immune chemokine and cytokine microenvironment, resulting in decreased cellular recruitment, proliferation, and activation at both the acute (7-d) and chronic (14-d) phases of the FBR. Further, we found that sustained NO release abrogated the implant-induced acute and chronic foreign body response through modulation of mRNA encoding for key immunological signaling molecules and pathways, including STAT1 and multiple STAT1 targets including MAPK14, IRAK4, MMP2, and CXCL10. The condition of diabetes promoted a more robust FBR to the implants, which was also controlled by sustained NO release. [ABSTRACT FROM AUTHOR]

Highlights: [•] Surface modification of silica nanoparticles to tune nitric oxide-release kinetics. [•] Hydrophobic modifications result in extended nitric oxide-release duration. [•] Method allows for reduced particle leaching from polymers. [Copyright &y& Elsevier]

The in vivo analytical performance of percutaneously implanted nitric oxide (NO)-releasing amperometric glucose biosensors was evaluated in swine for 10 A Needletype glucose biosensors were functionalized with NO-releasing polyurethane coatings designed to release similar total amounts of NO (3.1 μmol cm-2) for rapid (16.0 ± 4.4 h) or slower (>74.6 ± 16.6 h) durations and remain functional as outer glucose sensor membranes. Relative to controls, NO-releasing sensors were characterized with improved numerical accuracy on days 1 and 3. Furthermore, the clinical accuracy and sensitivity of rapid NO-releasing sensors were superior to control and slower NO-releasing sensors at both 1 and 3 d implantation. In contrast, the slower, extended, NO-releasing sensors were characterized by shorter sensor lag times (<4.2 min) in response to intravenous glucose tolerance tests versus burst NO-releasing and control sensors (>5.8 min) at 3, 7, and 10 d. Collectively, these results highlight the potential for NO release to enhance the analytical utility of in vivo glucose biosensors. Initial results also suggest that this analytical performance benefit is dependent on the NO-release duration. [ABSTRACT FROM AUTHOR]

Abstract: Secondary amine-functionalized chitosan oligosaccharides of different molecular weights (i.e., ∼2500, 5000, 10,000) were synthesized by grafting 2-methyl aziridine from the primary amines on chitosan oligosaccharides, followed by reaction with nitric oxide (NO) gas under basic conditions to yield N-diazeniumdiolate NO donors. The total NO storage, maximum NO flux, and half-life of the resulting NO-releasing chitosan oligosaccharides were controlled by the molar ratio of 2-methyl aziridine to primary amines (e.g., 1:1, 2:1) and the functional group surrounding the N-diazeniumdiolates (e.g., polyethylene glycol (PEG) chains), respectively. The secondary amine-modified chitosan oligosaccharides greatly increased the NO payload over existing biodegradable macromolecular NO donors. In addition, the water-solubility of the chitosan oligosaccharides enabled their penetration across the extracellular polysaccharides matrix of Pseudomonas aeruginosa biofilms and association with embedded bacteria. The effectiveness of these chitosan oligosaccharides at biofilm eradication was shown to depend on both the molecular weight and ionic characteristics. Low molecular weight and cationic chitosan oligosaccharides exhibited rapid association with bacteria throughout the entire biofilm, leading to enhanced biofilm killing. At concentrations resulting in 5-log killing of bacteria in Pseudomonas aeruginosa (P. aeruginosa) biofilms, the NO-releasing and control chitosan oligosaccharides elicited no significant cytotoxicity to mouse fibroblast L929 cells in vitro. [Copyright &y& Elsevier]

The active release of pharmaceutical agents and the use of porous sensor membranes represent the two most promising strategies for addressing the poor tissue biocompatibility of implantable glucose biosensors. Herein, we describe the combination of these approaches to create nitric oxide (NO)-releasing porous fiber mat-modified sensor membranes. An electrospinning method was used to directly modify needle-type glucose biosensors with the NO donor-loaded fibers. The resulting NO-releasing fiber mat (540 ± 139 nm fiber diameter, 94.1 ± 3.7% porosity) released ~100 nmol of NO per mg of polyurethane over 6 h while maintaining a porous structure without leaching of the NO donor, even in serum. The porous fiber membrane did not influence the analytical performance of the biosensor when ⩽50 μm thick. [ABSTRACT FROM AUTHOR]

The concentration of S-nitrosothiols (RSNOs), endogenous transporters of the signaling molecule nitric oxide (NO), fluctuate greatly in physiology often as a function of disease state. RSNOs may be measured indirectly by cleaving the S-N bond and monitoring the liberated NO. While ultraviolet photolysis and reductive-based cleavage both decompose RSNOs to NO, poor selectivity and the need for additional reagents preclude their utility clinically. Herein, we report the coupling of visible photolysis (i.e., 500-550 nm) and amperometric NO detection to quantify RSNOs with greater selectivity and sensitivity. Enhanced sensitivity (up to 1.56 nA μM-1) and lowered theoretical detection limits (down to 30 nM) were achieved for low molecular weight RSNOs (i.e., S-nitrosoglutathione, S-nitrosocysteine) by tuning the irradiation exposure. Detection of nitrosated proteins (i.e., S-nitrosoalbumin) was also possible, albeit at a decreased sensitivity (0.11 nA μM-1). This detection scheme was used to measure RSNOs in plasma and illustrate the potential of this method for future physiological studies. [ABSTRACT FROM AUTHOR]

The important biological roles of nitric oxide (NO) have prompted the development of analytical techniques capable of sensitive and selective detection of NO. Electrochemical sensing, more than any other NO detection method, embodies the parameters necessary for quantifying NO in challenging physiological environments such as blood and the brain. In this tutorial review, we provide a broad overview of the field of electrochemical NO sensors, including design, fabrication, and analytical performance characteristics. Both electrochemical sensors and biological applications are detailed. [ABSTRACT FROM AUTHOR]

The article offers a literature review and meta-analysis of electrochemical sensors articles published between January 2006 and January 2008. According to the authors, the field of electrochemical sensors is expanding and is of interest to a variety of disciplines beyond traditional chemistry. They emphasize articles with fundamental research on new chemical concepts rather than mere applications. They review research on potentiometric sensors, chronopotentiometric sensors, voltammetric sensors and electrochemical biosensors. They also discuss enzyme biosensors based on carbon nanotubes or nanoparticles and DNA biosensors.

Xerogel sensing films were synthesized via sol-gel chemistry were used to fabricate optical nitroxyl (HNO) sensors. Selective detection of HNO in solution was achieved by monitoring the rates of manganese(III) meso-tetrakis-(4-sulfonatophenyl) porphyrinate (MnIIITPPS) reductive nitrosylation in the anaerobic interior of aminoalkoxysilane-derived xerogel films. Nitroxyl permeability in sensor films deposited in round-bottom 96-well plates was enhanced via incorporation of trimethoxysilyl-terminated poly(amidoamine-organosilicon) dendrimers in the xerogel network. The selectivity of MnIIITPPS for HNO, the overall sensitivity, and the working dynamic range of the resulting sensors were characterized. The HNO-sensing microtiter plates were used to quantify pH-dependent HNO generation by the recently described HNO-donor sodium 1-(isopropylamino)diazene-1-ium-1,2-diolate (IPA/NO), and compare HNO production efficiency between IPA/NO and Angeli's salt, a traditional HNO-donor. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of a new nitric oxide (NO)-releasing scaffold prepared from amine-functionalized silica nanoparticles are reported. Inorganic-organic hybrid silica was prepared via cocondensation of tetraethoxy- or tetramethoxysilane (TEOS or TMOS) and aminoalkoxysilane with appropriate amounts of ethanol (or methanol), water, and ammonia. The amine functional groups in the silica were converted to N-diazeniumdiolate NO donors via exposure to high pressures of NO (5 atm) under basic conditions. Control over both the structure and concentration of the silane precursors (i.e., tetraalkoxy- and aminoalkoxysilanes) and specific synthetic conditions allowed for the preparation of NO donor silica particles of widely varying sizes (d = 20-500 nm), NO payloads (50-1780 nmol·mg-1), maximum amounts of NO released (10-5500 ppb·mg-1), half-lives (0.1-12 h), and NO release durations (up to 30 h). The silica nanoparticles were characterized by solid-state 29Si nuclear magnetic resonance (NMR), atomic force microscopy (AFM), elemental analysis, and gas adsorption-desorption isotherms. The advantages of silica-derived NO storage/delivery systems over previously reported macromolecular NO donors include the ability to (1) store large quantities of NO, (2) modulate NO release kinetics, and (3) readily tune particle size based on the composition of the particle. In addition, a one-pot strategy for preparing the NO donor silica allows for straightforward, high-throughput synthesis and purification. [ABSTRACT FROM AUTHOR]

A xerogel-based optical pH sensor capable of releasing low levels of nitric oxide (NO) and measuring changes in solution pH is reported. Through simple dip-coating procedures, aminoalkoxysilane-based xerogel films modified with N-diazeniumdiolate NO donor precursors and the fluorescent pH indicator seminaphthorhodamine-1 carboxylate (SNARF-1) were sequentially deposited onto optical fibers. The resulting sensors were characterized by fast and linear response to pH throughout the physiological range (pH 7.0-7.8). Real-time chemiluminescence measurements confirmed that the presence of the overlying SNARF-1-containing TMOS layer did not have an inhibitory effect on N-diazeniumdiolate formation or NO release, and the NO-releasing coatings were capable of maintaining NO fluxes >0.4 pmol/cm² s up to 16 h. In vitro blood compatibility studies using porcine platelets confirmed the expected thromboresistivity of the NO-releasing xerogel coatings. [ABSTRACT FROM AUTHOR]

To assess the benefits of nitric oxide (NO)-releasing sol–gels as potential antibacterial coatings for orthopedic devices, medical-grade stainless steel is coated with a sol–gel film of 40% N-aminohexyl-N-aminopropyltrimethoxysilane and 60% isobutyltrimethoxysilane. Upon converting the diamine groups in these films to diazeniumdiolate NO donors, the NO release from the sol–gel-coated stainless steel is evaluated at both ambient and physiological temperature. Sol–gel films incubated at 25°C have a lower NO flux over the first 24 h compared to those at 37°C, but release more than five times longer. The bacterial adhesion resistance of NO-releasing coatings is evaluated in vitro by exposing bare steel, sol–gel, and NO-releasing sol–gel-coated steel to cell suspensions of Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis at 25°C and 37°C. Cell adhesion to bare and sol–gel-coated steel is similar, while NO-releasing surfaces have significantly less bacterial adhesion for all species and temperatures investigated. [Copyright &y& Elsevier]

A hybrid sol-gel/polyurethane glucose biosensor that releases nitric oxide is developed and characterized. The biosensor consists of a platinum electrode coated with four polymeric membranes including the following: (1) sol-gel with immobilized glucose oxidase (GOx); (2) polyurethane to protect the enzyme; (3) NO donor-modified sol-gel particle-doped polyurethane; and (4) polyurethane. This configuration was developed due to the drastic reduction in sensitivity observed for NO donor-modified sol-gel film-based glucose sensors. For the hybrid sol-gel/polyurethane biosensor, sol-gel particles are first modified with the NO donor and then incorpo- rated into a polyurethane layer that is coated onto the preimmobilized GOx electrode. In this manner, the GOx layer is not exposed to the harsh conditions necessary to impart NO release ability to the biosensor, and only a minimal decrease in sensitivity due to the NO release is observed. The glucose response of the NO-releasing glucose biosensor and its NO generation profiles are reported. In addition, the stability of the sol-gel particles in the supporting polyurethane membrane is discussed. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) release from S -nitrosothiol-modified mesoporous silica nanoparticles imbedded in the diffusion limiting layer of a glucose sensor has been demonstrated as an effective strategy for mitigating the foreign body response common to sensor implantation, resulting in improved analytical performance. With respect to potential clinical translation of this approach, the effects of sterilization on NO-releasing biosensors require careful evaluation, as NO donor chemistry is sensitive to temperature and environment. Herein, we evaluated the influence of multiple sterilization methods on 1) sterilization success; 2) NO payload; and 3) sensor performance to establish the commercialization potential of NO-releasing glucose sensors. Sensors were treated with ethylene oxide gas, the most common sterilization method for intricate medical devices, which led to undesirable (i.e., premature) release of NO. To reduce NO loss, alternative sterilization methods that were studied included exposure to ultraviolet (UV) light and immersion in 70 % ethanol (EtOH). Sterilization cycle times required to reach a 10−6 sterility assurance level were determined for both UV light and 70 % EtOH against Gram-negative and -positive bacteria. The longest sterilization cycle times (258 s and 628 s for 70 % EtOH and UV light, respectively) resulted in a negligible impact on benchtop sensor performance. However, sterilization with 70 % ethanol resulted in a reduced NO-release duration. Ultraviolet light exposure for ∼10 min proved successful at eliminating bacteria without compromising NO payloads or durations and presents as the most promising method for sterilization of these sensors. In addition, storage of NO-releasing sensor membranes at –20 and –80 °C resulted in preservation of NO release for 6 and 12 months, respectively. • Ethylene oxide gas sterilization negatively impacts nitric oxide payloads. • Nitric oxide payloads maintained after UVC exposure. • UVC light exposure for only 10 min results in a 12-log reduction in bacteria counts. • Nitric oxide-releasing glucose biosensors can be stored for at least 12 months at –80 ºC. [ABSTRACT FROM AUTHOR]

This study investigates the antibiofilm action of nitric oxide (NO)-releasing hyperbranched polymers against ex vivo multispecies periodontal biofilms. The antibiofilm efficacy of NO-releasing hyperbranched polymers was evaluated as a function of NO-release properties, polymer concentrations, and oxygen levels in the exposure media. 16s rRNA sequencing technique was employed to evaluate the impact of NO-releasing hyperbranched polymers on the microbial composition of the biofilms. The addition of NO release significantly improved the antibiofilm action of the hyperbranched polymers, with NO-releasing hyperbranched polyamidoamines of largest NO payloads being more effective than hyperbranched polykanamycins. Furthermore, the NO-releasing hyperbranched polymers reduced the biofilm metabolic activity in a dose-dependent manner, killing biofilm-detached bacteria under both aerobic and anaerobic conditions, with greater antimicrobial efficacy observed under aerobic conditions. These results demonstrate for the first time the potential therapeutic utility of NO-releasing hyperbranched polymers for treating multispecies dental biofilms. [ABSTRACT FROM AUTHOR]

Low and high molecular weight alginate biopolymers were chemically modified to store and release potentially therapeutic levels of nitric oxide (NO). Carbodiimide chemistry was first used to modify carboxylic acid functional groups with a series of small molecule alkyl amines. The resulting secondary amines were subsequently converted to N-diazeniumdiolate NO donors via reaction with NO gas under basic conditions. NO donor-modified alginates stored between 0.4-0.6 μmol NO·mg-1. In aqueous solution, the NO-release kinetics were diverse (0.3-13 h half-lives), dependent on the precursor amine structure. The liberated NO showed bactericidal activity against Pseudomonas aeruginosa and Staphylococcus aureus with pathogen eradication efficiency dependent on both molecular weight and NO-release kinetics. The combination of lower molecular weight (∼5 kDa) alginates with moderate NO-release durations (half-life of ∼4 h) resulted in enhanced killing of both planktonic and biofilm-based bacteria. Toxicity against human respiratory epithelial (A549) cells proved negligible at NO-releasing alginate concentrations required to achieve a 5-log reduction in viability in the biofilm eradication assay. [ABSTRACT FROM AUTHOR]

The foreign body response (FBR) to nitric oxide (NO)-releasing subcutaneous implants was compared between healthy and streptozotocin-induced diabetic swine by evaluating inflammation, collagen capsule formation, and angiogenesis. Steel wire substrates were first modified with polyurethane membranes capable of diverse NO-release kinetics (NO fluxes and release durations of 0.8–630.0 pmol cm −2 s −1 and 2–13 d, respectively). The NO-releasing materials were implanted in the subcutis for 3, 10, or 25 d for histological and immunohistochemical evaluation of the FBR. A delayed, more severe inflammatory response to control (i.e., non-NO-releasing) implants was observed in diabetic pigs relative to healthy swine. Regardless of the animal disease state, each NO-releasing implant tested elicited reduced inflammation compared to controls at both 3 and 10 d. However, only the NO-release materials capable of releasing low NO fluxes (0.8–3.3 pmol cm −2 s −1 ) for 7–13 d durations mitigated the inflammatory response at 25 d. Using immunohistochemical staining for the endothelial cell surface marker CD-31, we also observed poor blood vessel development at non-NO-releasing implants in diabetic swine. Relative to controls, NO-releasing implants with the longest NO-release duration (13 d) increased blood vessel densities by 47.1 and 70.4% in the healthy and diabetic pigs, respectively. In the healthy model, tissues surrounding the long NO-release materials contained sparse amounts of collagen, whereas implants with shorter NO-release durations (2, 3, and 7 d) were characterized with a dense collagen encapsulation layer, similar to controls. Collagen deposition in diabetic swine was inhibited, and unaffected by NO. These results emphasize several key differences in the FBR in the setting of acute onset diabetes. The observation that NO release counteracts the more severe FBR in diabetic swine while simultaneously promoting tissue integration may help guide the design of medical implants (e.g., glucose sensors) with improved performance for diabetes management. [ABSTRACT FROM AUTHOR]

This article focuses on the synthesis of nitric oxide-releasing gold nanoparticles. The astounding pace of discovery on the bioregulatory roles of nitric oxide (NO) demands new methods for generating NO in a controlled manner to facilitate both an improved understanding of NO's function in physiology and the development of NO-associated therapies. Monolayer-protected cluster (MPC) gold nanoparticles, or MPCs, have received much attention due to their unique size, stability, and highly functional design. Gold nanoparticles were synthesized by the reaction of hydrogen tetrachloroaurate salt with hexanethiol in the presence of sodium borohydride. The size and stability of the gold nanoparticles were characterized using thermal gravimetric analysis, UV-vis spectroscopy, and transmission electron microscopy.

Purpose: Burn is associated with severe immune dysfunction, including an anti-inflammatory state that occurs late after burn. While increased nitric oxide (NO) production is associated with severe infection and sepsis, the effect of burn trauma on these levels during a non-lethal infection remains unknown. We hypothesized that in a mouse model, (1) NO levels would be increased after infection without trauma and (2) burn would lead to decreased NO production even during infection.Methods: Mice were infected via intra-tracheal inoculation with Pseudomonas aeruginosa 14 d following a 20% total body surface area contact burn. At 48h following infection, blood was drawn to quantify NO concentrations using a microfluidic electrochemical sensor.Significant Findings: In uninjured mice, infection caused a significant increase in blood NO levels. Increases in NO occurred in a dose-dependent response to the bacterial inoculum. Following burn, an identical infection did not elicit increases in NO.Conclusions: While increases in NO are expected over the course of an infection without prior trauma, burn and subsequent immune suppression decreases NO levels even in the presence of infection. [ABSTRACT FROM AUTHOR]

A seriesof amphiphilic nitric oxide (NO)-releasing poly(amidoamine)(PAMAM) dendrimers with different exterior functionalities were synthesizedby a ring-opening reaction between primary amines on the dendrimerand propylene oxide (PO), 1,2-epoxy-9-decene (ED), or a ratio of thetwo, followed by reaction with NO at 10 atm to produce N-diazeniumdiolate-modified scaffolds with a total storage of ∼1μmol/mg. The hydrophobicity of the exterior functionality wastuned by varying the ratio of PO and ED grafted onto the dendrimers.The bactericidal efficacy of these NO-releasing vehicles against establishedGram-negative Pseudomonas aeruginosabiofilms was then evaluated as a function of dendrimer exteriorhydrophobicity (i.e., ratio of PO/ED), size (i.e., generation), andNO release. Both the size and exterior functionalization of dendrimerproved important to a number of parameters including dendrimer−bacteriaassociation, NO delivery efficiency, bacteria membrane disruption,migration within the biofilm, and toxicity to mammalian cells. Althoughenhanced bactericidal efficacy was observed for the hydrophobic chains(e.g., ED), toxicity to L929 mouse fibroblast cells was also notedat concentrations necessary to reduce bacterial viability by 5-logs(99.999% killing). The optimal PO to ED ratios for biofilm eradicationwith minimal toxicity against L929 mouse fibroblast cells were 7:3and 5:5. The study presented herein demonstrated the importance ofboth dendrimer size and exterior properties in determining efficacyagainst established biofilms without compromising biocompatibilityto mammalian cells. [ABSTRACT FROM AUTHOR]

Standard photolithographic techniques and a nitric oxide (NO) selective xerogel polymer were utilized to fabricate an amperometric NO microfluidic sensor with low background noise and the ability to analyze NO levels in small sample volumes (~250 μL). The sensor exhibited excellent analytical performance in phosphate buffered saline, including a NO sensitivity of 1.4 pA nM-1, a limit of detection (LOD) of 840 pM, and selectivity over nitrite, ascorbic acid, acetaminophen, uric acid, hydrogen sulfide, ammonium, ammonia, and both protonated and deprotonated peroxynitrite (selectivity coefficients of -5.3, -4.2, -4.0, -5.0, -6.0, -5.8, -3.8, -1.5, and -4.0, respectively). To demonstrate the utility of the microfluidic NO sensor for biomedical analysis, the device was used to monitor changes in blood NO levels during the onset of sepsis in a murine pneumonia model. [ABSTRACT FROM AUTHOR]

The article discusses the advancements in the development of continuous glucose monitoring technologies that are used to monitor blood glucose level and also reflects on the use of biocompatible materials in the electro-chemical glucose sensors in devices. It also reflects on the challenges associated with the development of biocompatible coatings for glucose sensors. It mentions several techniques for glucose monitoring such as iontophoresis, microdialysis and optical coherence tomography.

Despite growing reports on the biological action of nitric oxide (NO) as a function of NO payload, the validity of such work is often questionable due to the manner in which NO is measured and/or the solution composition in which NO is quantified. To highlight the importance of measurement technique for a given sample type, NO produced from a small-molecule NO donor (N-diazeniumdiolated l-proline, PROLI/NO) and a NO-releasing xerogel film were quantified in a number of physiological buffers and fluids, cell culture media, and bacterial broth by the Griess assay, a chemiluminescence analyzer, and an amperometric NO sensor. Despite widespread use, the Griess assay proved to be inaccurate for measuring NO in many of the media tested. In contrast, the chemiluminescence analyzer provided superb kinetic information in most buffers but was impractical for NO analysis in proteinaceous media. The electrochemical NO sensor enabled greater flexibility across the various media with potential for spatial resolution, albeit at lower than expected NO totals versus either the Griess assay or chemiluminescence. The results of this study highlight the importance of measurement strategy for accurate NO analysis and reporting NO-based biological activity. [ABSTRACT FROM AUTHOR]

The antibacterial activity of a series of nitric oxide(NO)-releasingpoly(propylene imine) (PPI) dendrimers was evaluated against bothGram-positive and Gram-negative pathogenic bacteria, including methicillin-resistant Staphylococcus aureus. A direct comparison of thebactericidal efficacy between NO-releasing and control PPI dendrimers(i.e., non-NO-releasing) revealed both enhanced biocidal action ofNO-releasing dendrimers and reduced toxicity against mammalian fibroblastcells. Antibacterial activity for the NO donor-functionalized PPIdendrimers was shown to be a function of both dendrimer size (molecularweight) and exterior functionality. In addition to minimal toxicityagainst fibroblasts, NO-releasing PPI dendrimers modified with styreneoxide exhibited the greatest biocidal activity (≥99.999% killing)against all bacterial strains tested. The N-diazeniumdiolateNO donor-functionalized PPI dendrimers presented in this study holdpromise as effective NO-based therapeutics for combating bacterialinfections. [ABSTRACT FROM AUTHOR]