Nitric Oxide Sensor Research Articles

Waveguide-Based Microwave Nitric Oxide Sensor for COVID-19 Screening: Mass Transfer Modulation Effect on Hollow Confined WO3 Structures.

Serious acute respiratory syndrome coronavirus-2 (SARS-CoV-2) poses a tremendous threat to global public health. Recently, the Food and Drug Administration approved the emergency use of volatile organic components as detection biomarkers for COVID-19, ushering in a new era of portable, simple, and rapid epidemiological screening based on breath diagnosis. Nitric oxide (NO) is an important biomarker indicating the degree of inflammation in the respiratory tract. In this study, a hollow multishelled structured WO3 (HoMSs-WO3)-based waveguide microwave gas sensor (MGS) was fabricated to detect trace levels of NO in exhaled breath for the preliminary diagnosis of COVID-19. The sensor showed excellent reusability and selectivity and efficiently detected NO in the 10-100 ppb, with a sensitivity of 39.27 dB/ppm and a detection limit of 2.52 ppb. In addition, a sound correlation was observed in the measurement results between the MGS and the Sunvou detector for detecting NO from the exhaled breath of clinical COVID-19 patients. The difference between the two measurements was within 1.96 standard bias, and the consistency range was -12 to 17 ppb, thus fully demonstrating the significant potential of the sensor in COVID-19 screening.

Enhancement of nitric oxide sensing performance via oxygen vacancy promotion on strontium-doped LaFeO3 perovskites

The potential of Sr-doped LaFeO3 as a nitrogen oxide–sensing material was studied by experimentation and theory calculation. The test results showed a much higher sensitivity and selectivity for a nitric oxide sensor based on Sr-doped LaFeO3 than on pure LaFeO3. The response, which was increased nearly 0.5-fold compared to pure LaFeO3, was attributed to an enhancement of oxygen vacancy and adsorbed oxygen. Further theoretical analysis indicated that Sr doping resulted in the formation of oxygen vacancy defects and altered the adsorption energy of the material, leading to an increase in chemisorbed oxygen species and intermolecular interactions. This work emphasizes the significance of oxygen vacancy defects in gas sensors and provides a feasible approach for enhancing the properties of gas sensors.

Red light mediates the exocytosis of vasodilatory vesicles from cultured endothelial cells: a cellular, and ex vivo murine model

We have previously established that 670 nm energy induces relaxation of blood vessels via an endothelium derived S-nitrosothiol (RSNO) suggested to be embedded in vesicles. Here, we confirm that red light facilitates the exocytosis of this vasodilator from cultured endothelial cells and increases ex vivo blood vessel diameter. Ex vivo pressurized and pre-constricted facial arteries from C57Bl6/J mice relaxed 14.7% of maximum diameter when immersed in the medium removed from red-light exposed Bovine Aortic Endothelial Cells. In parallel experiments, 0.49 nM RSNO equivalent species was measured in the medium over the irradiated cells vs dark control. Electron microscopy of light exposed endothelium revealed significant increases in the size of the Multi Vesicular Body (MVB), a regulator of exosome trafficking, while RSNO accumulated in the MVBs as detected with immunogold labeling electron microscopy (1.8-fold of control). Moreover, red light enhanced the presence of F-actin related stress fibers (necessary for exocytosis), and the endothelial specific marker VE-cadherin levels suggesting an endothelial origin of the extracellular vesicles. Flow cytometry coupled with DAF staining, an indirect sensor of nitric oxide (NO), indicated significant amounts of NO within the extracellular vesicles (1.4-fold increase relative to dark control). Therefore, we further define the mechanism on the 670 nm light mediated traffic of endothelial vasodilatory vesicles and plan to leverage this insight into the delivery of red-light therapies.Graphical abstract

Low Part-Per-Trillion, Humidity Resistant Detection of Nitric Oxide Using Microtoroid Optical Resonators.

The nitric oxide radical plays pivotal roles in physiological as well as atmospheric contexts. Although the detection of dissolved nitric oxide in vivo has been widely explored, highly sensitive (i.e., low part-per-trillion level), selective, and humidity-resistant detection of gaseous nitric oxide in air remains challenging. In the field, humidity can have dramatic effects on the accuracy and selectivity of gas sensors, confounding data, and leading to overestimation of gas concentration. Highly selective and humidity-resistant gaseous NO sensors based on laser-induced graphene were recently reported, displaying a limit of detection (LOD) of 8.3 ppb. Although highly sensitive (LOD = 590 ppq) single-wall carbon nanotube NO sensors have been reported, these sensors lack selectivity and humidity resistance. In this report, we disclose a highly sensitive (LOD = 2.34 ppt), selective, and humidity-resistant nitric oxide sensor based on a whispering-gallery mode microtoroid optical resonator. Excellent analyte selectivity was enabled via novel ferrocene-containing polymeric coatings synthesized via reversible addition-fragmentation chain-transfer polymerization. Utilizing a frequency locked optical whispering evanescent resonator system, the microtoroid's real-time resonance frequency shift response to nitric oxide was tracked with subfemtometer resolution. The lowest concentration experimentally detected was 6.4 ppt, which is the lowest reported to date. Additionally, the performance of the sensor remained consistent across different humidity environments. Lastly, the impact of the chemical composition and molecular weight of the novel ferrocene-containing polymeric coatings on sensing performance was evaluated. We anticipate that our results will have impact on a wide variety of fields where NO sensing is important such as medical diagnostics through exhaled breath, determination of planetary habitability, climate change, air quality monitoring, and treating cardiovascular and neurological disorders.

Nitric oxide sensor NsrR is the key direct regulator of magnetosome formation and nitrogen metabolism in Magnetospirillum.

Nitric oxide (NO) plays an essential role as signaling molecule in regulation of eukaryotic biomineralization, but its role in prokaryotic biomineralization is unknown. Magnetospirillum gryphiswaldense MSR-1, a model strain for studies of prokaryotic biomineralization, has the unique ability to form magnetosomes (magnetic organelles). We demonstrate here that magnetosome biomineralization in MSR-1 requires the presence of NsrRMg (anNO sensor) and a certain level of NO. MSR-1 synthesizes endogenous NO via nitrification-denitrification pathway to activate magnetosome formation. NsrRMg was identified as a global transcriptional regulator that acts as a direct activator of magnetosome gene cluster (MGC) and nitrification genes but as a repressor of denitrification genes. Specific levels of NO modulate DNA-binding ability of NsrRMg to various target promoters, leading to enhancing expression of MGC genes, derepressing denitrification genes, and repressing nitrification genes. These regulatory functions help maintain appropriate endogenous NO level. This study identifies for the first time the key transcriptional regulator of major MGC genes, clarifies the molecular mechanisms underlying NsrR-mediated NO signal transduction in magnetosome formation, and provides a basis for a proposed model of the role of NO in the evolutionary origin of prokaryotic biomineralization processes.

The histidine kinase NahK regulates pyocyanin production through the PQS system.

Many bacterial histidine kinases work in two-component systems that combine into larger multi-kinase networks. NahK is one of the kinases in the GacS Multi-Kinase Network (MKN), which is the MKN that controls biofilm regulation in the opportunistic pathogen Pseudomonas aeruginosa. This network has also been associated with regulating many virulence factors P. aeruginosa secretes to cause disease. However, the individual role of each kinase is unknown. In this study, we identify NahK as a novel regulator of the phenazine pyocyanin (PYO). Deletion of nahK leads to a fourfold increase in PYO production, almost exclusively through upregulation of phenazine operon two (phz2). We determined that this upregulation is due to mis-regulation of all P. aeruginosa quorum-sensing (QS) systems, with a large upregulation of the Pseudomonas quinolone signal system and a decrease in production of the acyl-homoserine lactone-producing system, las. In addition, we see differences in expression of quorum-sensing inhibitor proteins that align with these changes. Together, these data contribute to understanding how the GacS MKN modulates QS and virulence and suggest a mechanism for cell density-independent regulation of quorum sensing. IMPORTANCE Pseudomonas aeruginosa is a Gram-negative bacterium that establishes biofilms as part of its pathogenicity. P. aeruginosa infections are associated with nosocomial infections. As the prevalence of multi-drug-resistant P. aeruginosa increases, it is essential to understand underlying virulence molecular mechanisms. Histidine kinase NahK is one of several kinases in P. aeruginosa implicated in biofilm formation and dispersal. Previous work has shown that the nitric oxide sensor, NosP, triggers biofilm dispersal by inhibiting NahK. The data presented here demonstrate that NahK plays additional important roles in the P. aeruginosa lifestyle, including regulating bacterial communication mechanisms such as quorum sensing. These effects have larger implications in infection as they affect toxin production and virulence.

Gold Nanoparticle Sensitized Zinc Oxide Nanorods-Based Nitric Oxide Gas Sensors with High Sensitivity, Selectivity and Low Detection Limit

Development of a low-cost hand-held nitric oxide (NO) sensor with high selectivity, sensitivity and low detection limit is attractive for environment and health monitoring applications. NO gas sensor was fabricated using hydrothermally grown ZnO nanorods (ZnO NRs). The sensing performance like sensor response, sensitivity, detection limit has been improved significantly by attaching gold nanoparticles (Au NPs) with ZnO NRs. Au NPs were synthesized by chemical reduction method from gold chloride trihydrate. The attachment of Au NPs on nanorods was done by spin coating method. The maximum sensor response and sensitivity were obtained at [Formula: see text]C operating temperature with [Formula: see text]l gold loading. The interference study of the sensor was carried out with acetone, ammonia, carbon monoxide, hydrogen peroxide and propanol. It demonstrated high selectivity towards the interfering gases and high humid condition. Au-decorated ZnO NRs exhibited very low detection limit [Formula: see text][Formula: see text]ppb, which is attractive for biomedical applications.

(Invited) Directed Evolution and Machine Learning for Improved ssDNA-SWCNTs Sensor for Nitric Oxide Detection

Single-walled carbon nanotubes (SWCNTs) show great potential for biosensing applications due to their unique optical properties. SWCNTs emit fluorescence in the near-infrared (NIR) region that is stable, biotransparent, and highly sensitive to changes in their environment. The biocompatibility and the selectivity of their interactions can be engineered through SWCNT surface functionalization. One of the most common functionalization approaches is the non-covalent wrapping of SWCNTs with single-stranded DNA (ssDNA). Though the ssDNA sequences can be varied to control the optical response of these SWCNT sensors, the dependence of the optical response on the sequence is unknown and unpredictable. This lack of information on the relationship between the ssDNA sequence and sensor performance is a major bottleneck in engineering SWCNT-based optical sensors.In this work, we develop a guided approach to engineer optical ssDNA-SWCNT sensors. Using a combination of machine learning and directed evolution[1], we designed an optical sensor for nitric oxide (NO), a pro-inflammatory mediator that induces inflammation[2]. We demonstrate a 7-fold enhancement in sensor response compared to the state-of-the-art sensor based on the (AT)15 sequence[3]. This approach thus provides a powerful means of overcoming existing bottlenecks in SWCNT sensor design, ushering a new generation of near-infrared technologies for biomedical research and clinical diagnostics.

Tetrazine-Based Ratiometric Nitric Oxide Sensor Identifies Endogenous Nitric Oxide in Atherosclerosis Plaques by Riding Macrophages as a Smart Vehicle.

Atherosclerosis (AS) is the formation of plaques in blood vessels, which leads to serious cardiovascular diseases. Current research has disclosed that the formation of AS plaques is highly related to the foaming of macrophages. However, there is a lack of detailed molecular biological mechanisms. We proposed a "live sensor" by grafting a tetrazine-based ratiometric NO probe within macrophages through metabolic and bio-orthogonal labeling. This "live sensor" was proved to target the AS plaques with a diameter of only tens of micrometers specifically and visualized endogenous NO at two lesion stages in the AS mouse model. The ratiometric signals from the probe confirmed the participation of NO during AS and indicated that the generation of endogenous NO increased significantly as the lesion progressed. Our proposal of this "live sensor" provided a native and smart strategy to target and deliver small molecular probes to the AS plaques at the in vivo level, which can be used as universal platforms for the detection of reactive molecules or microenvironmental factors in AS.

Employing graphene nanocomposites as nitric oxide sensors

Graphene composites offer high sensitivities, low detection limits, and fast responses for real-time biochemical monitoring.

High-selectivity terahertz metamaterial nitric oxide sensor based on ZnTiO3 perovskite membrane

Human exhaled gases contain a wide range of volatile organic compounds, offering the potential for detecting physiological, cardiovascular, and endocrine disorders. For instance, nitric oxide (NO) concentration can be indicative of chronic obstructive pulmonary disease. Analyzing exhaled gases provides a noninvasive approach to disease detection without posing any risks to individuals. While electronic sensors have been developed over the past two decades for NO detection at high temperatures, few studies have explored optical detection in the ultraviolet to visible light range, which may have adverse effects on the skin. In this study, we designed a split-ring resonator metamaterial tailored for operation within the terahertz (THz) frequency range. Specifically, the metamaterial was designed to resonate at the NO frequency of 0.257 THz. To enhance gas absorption capacity, we incorporated a composite film layer consisting of ZnTiO3 and reduced graphene oxide onto the metamaterial. By sintering ZnTiO3 powder at different temperatures, we achieved an increase in component sensitivity (ΔT/T) from 2% to 16.4%. Overall, the proposed metamaterial holds promise for both physical monitoring applications and the development of wearable electronic devices.

Biotemplate-inherited porous SnO2 monotubes with oxygen vacancies for ultra-high response and fast detection of nitric oxide at low temperature

How to construct low-temperature nitric oxide sensors with fast detecting speed and high sensing response remains challenging. To this end, we simply immersed the waste willow catkins in SnCl4 solution, and then calcined the precursors to controllably prepare biotemplate-inherited SnO2 sensing materials. Amongst, the monotubes (marked as SnO2-6) obtained by calcination at 600 °C are cross-linked by small-size nanoparticles, and have homogeneous distribution of mesopores, large specific surface area and rich oxygen vacancies. Synergistic effect of these advantageous structure characteristics greatly accelerates the rapid diffusion of gas molecules in sensing layer, and exposes more surface-active sites to promote their adsorption and chemical reaction, thus ultra-highly and rapidly monitoring NO at low temperature. At 92 °C, SnO2-6 sensor exhibits large response value of 2533 towards 10 ppm NO, which is 15.73 times higher than that of SnO2-7 material. Its response/recovery times are shortened to 49 s/13 s. Meanwhile, it still possesses small practical limit of detection, satisfactory selectivity, long-term stability and moisture resistance. Furthermore, the sensing mechanism was analyzed in detail.

Gold Nanoparticle-Modified Tungsten Oxide Flakes as Nitric Oxide Sensor Electrodes for Fruit Quality Monitoring

Development of low-cost, handheld nitric oxide (NO) sensors is very much important due to its major role in environmental pollution, biomedical research, and food safety applications. In this study, an electrochemical NO sensor has been fabricated using gold nanoparticle (Au NP)-modified tungsten oxide (WO3) nanoflakes. WO3 nanoflakes were grown hydrothermally on fluorine doped tin oxide (FTO) substrates, and Au NPs were attached by a photoreduction method. The sensing characteristics of pristine WO3 and Au NP-coated WO3 electrodes have been studied by amperometric techniques. The sensor performance has been optimized at various Au NP loadings. The optimized sensor demonstrated a high sensitivity (∼39.37 μA cm–2 mM–1) over a wide linear range (∼10 μM to 5.78 mM) with a low detection limit (∼0.12 μM). The Au NP-coated WO3 sensing electrode demonstrated high stability. The sensor current only decreases 7.54% after 31 days of continuous measurements. The sensor also showed fast response (1.7 s) and high selectivity toward NO detection. NO detection in fruit samples (apple and orange) has been studied with the Au NP-modified WO3 electrode for fruit quality monitoring application.

Low-Cost Nitric Oxide Sensors: Assessment of Temperature and Humidity Effects.

High equipment cost is a significant entry barrier to research for small organizations in developing solutions to air pollution problems. Low-cost electrochemical sensors show sensitivity at parts-per-billion by volume mixing ratios but are subject to variation due to changing environmental conditions, in particular temperature. In this study, we demonstrate a low-cost Internet of Things (IoT)-based sensor system for nitric oxide analysis. The sensor system used a four-electrode electrochemical sensor exposed to a series of isothermal/isohume conditions. When deployed under these conditions, stable baseline responses were achieved, in contrast to ambient air conditions where temperature and humidity conditions may be variable. The interrelationship between working and auxiliary electrodes was linear within an environmental envelope of 20-40 °C and 30-80% relative humidity, with correlation coefficients from 0.9980 to 0.9999 when measured under isothermal/isohume conditions. These data enabled the determination of surface functions that describe the working to auxiliary electrode offsets and calibration curve gradients and intercepts. The linear and reproducible nature of individual calibration curves for stepwise nitric oxide (NO) additions under isothermal/isohume environments suggests the suitability of these sensors for applications aside from their role in air quality monitoring. Such applications would include nitric oxide kinetic studies for atmospheric applications or measurement of the potential biocatalytic activity of nitric oxide consuming enzymes in biocatalytic coatings, both of which currently employ high-capital-cost chemiluminescence detectors.

Nitric Oxide Sensing by a Blue Fluorescent Protein.

S-Nitrosylation of cysteine residues is an important molecular mechanism for dynamic, post-translational regulation of several proteins, providing a ubiquitous redox regulation. Cys residues are present in several fluorescent proteins (FP), including members of the family of Aequorea victoria Green Fluorescent Protein (GFP)-derived FPs, where two highly conserved cysteine residues contribute to a favorable environment for the autocatalytic chromophore formation reaction. The effect of nitric oxide on the fluorescence properties of FPs has not been investigated thus far, despite the tremendous role FPs have played for 25 years as tools in cell biology. We have examined the response to nitric oxide of fluorescence emission by the blue-emitting fluorescent protein mTagBFP2. To our surprise, upon exposure to micromolar concentrations of nitric oxide, we observed a roughly 30% reduction in fluorescence quantum yield and lifetime. Recovery of fluorescence emission is observed after treatment with Na-dithionite. Experiments on related fluorescent proteins from different families show similar nitric oxide sensitivity of their fluorescence. We correlate the effect with S-nitrosylation of Cys residues. Mutation of Cys residues in mTagBFP2 removes its nitric oxide sensitivity. Similarly, fluorescent proteins devoid of Cys residues are insensitive to nitric oxide. We finally show that mTagBFP2 can sense exogenously generated nitric oxide when expressed in a living mammalian cell. We propose mTagBFP2 as the starting point for a new class of genetically encoded nitric oxide sensors based on fluorescence lifetime imaging.

Graphitic carbon-doped SnO2 nanosheets-wrapped tubes for chemiresitive ppb-level nitric oxide sensors operated near room temperature

The development of low-temperature metal oxide-based sensors with high sensing response towards harmful ppb-level gases remains challenging. Based on the idea of biological structure imitation, we choose wooden hydrangea petals as biotemplate and carbon source to controllably replicate graphitic carbon-doped SnO2 material (GC/SnO2-6) by simply calcining the salt solution-soaked precursor at 600 °C. Its morphology is tube bundle wrapped by corrugated sheets that formed by cross-linkage of nanoparticles. The internal surface of tube wall is decorated with nanoaggregates. The fabricated GC/SnO2-6 sensor exhibits response value of 256.3 towards 1 ppm NO at 50 ℃, which is 9.9 times higher than that (S = 26.0) of pure SnO2-7 material obtained by calcining at 700 ℃ in air. Meanwhile, this sensor also has short recovery time (42 s), low actual detection limit (50 ppb), satisfactory moisture resistance and long-term stability. Such excellent comprehensive gas-sensing performance is attributed to the homogeneous mesopore and large specific surface area of its biomorphic structure, as well as the synergism of graphitic carbon doping and abundant oxygen vacancies. In addition, the enhanced sensing mechanism is also explored in detail.

Design, synthesis and evaluation of 15N- and 13C-labeled molecular probes as hyperpolarized nitric oxide sensors

[Display omitted] Nitric oxide (NO) is an important signaling molecule involved in a wide range of biological processes. Development of non-invasive, real-time detection of NO is greatly desired yet remains challenging. Here we report the design and development of novel 15N- and 13C-labeled NO-sensing probes for hyperpolarized nuclear magnetic resonance (HP-NMR) studies. These probes undergo selective and rapid reaction with NO to generate in situ AZO-products that can be monitored with distinguishable NMR signals as a read-out. This study also allows for a direct comparison of the 15N and 13C nuclei performances in hyperpolarized reaction-based probes. The simple and general SABRE-SHEATH hyperpolarization method works on the 15N- and 13C-NO-sensing probes. Measured long spin–lattice relaxation (T1) values, especially for 15N-NO probes, will allow for real-time reaction-based imaging of NO.

Highly sensitive and selective nitric oxide sensor based on biomorphic ZnO microtubes with dual-defects assistance at low temperature

Fabrication of diverse surface defects-assisted metal oxide materials is an effective avenue to achieve rapid and accurate detection of harmful gases. Herein, through the confinement effect of tracheids and vesicles in cajuput bark template, biomorphic ZnO hierarchical materials (ZnO-6) constructed from spherical nanoparticles were simply synthesized by zinc salt immersion and calcination at 600 °C in air. Porous ZnO-6 microtubes can greatly improve the rapid transmission and desorption behavior of target gas. Especially, the presence of electron donor dual-defects oxygen vacancy (VO) and zinc interstitial (Zni) can provide more active sites for surface gas adsorption and chemical reactions, thus effectively enhancing the detection ability of ZnO sensing material to toxic NO gas. At a low operating temperature of 92 °C, the high response value of 118 to 10 ppm NO for ZnO-6 sensor is 5.4 times higher than that of as-synthesized template-free ZnO-0 nanoparticles, and also represents the highest response among reported metal oxide-based gas sensors at low energy consumption. Meanwhile, this sensor has rapid recovery characteristic, good selectivity, long-term stability and moisture resistance. Moreover, the surface defects and their induced sensing mechanism are also characterized and explored.

Molecular engineering-based a dual-responsive fluorescent sensor for sulfur dioxide and nitric oxide detecting in acid rain and its imaging studies in biosystems

Sulfur dioxide (SO2) and nitric oxide (NO), known as sulfur oxides and nitrogen oxides, are toxic air pollutants and seriously threaten human health. Herein, for the first time, a robust dual-response fluorescent sensor CGT with two different emission fluorophores and dual well-known response-group for visual bisulphites (HSO3-) and nitrites (NO2-) detection was reported. Specifically, once CGT was incubated with HSO3- firstly, the color of the test solution changed to dark yellow with no-fluorescence emission, following added NO2-, the color of the test solution changed to yellow with a bright cyan emission. However, NO2- was added firstly, the color of the test solution changed to dark purple with a white emission, and then added HSO3-, the color of the test solution changed to yellow with a bright cyan emission. Furthermore, CGT showed high sensitivity and selectivity toward HSO3- and NO2- detecting with good detection limits as low as 20.17 nM and 4.14 nM, respectively. Impressively, CGT showed good detection capability in complex aqueous samples and was successfully used for the detection of HSO3- and NO2- in biosystems. Thus, the experimental results indicated CGT as a powerful novel visual detecting tool for HSO3- and NO2- detecting in complex acid rain and biosystems.

Low temperature detection of nitric oxide by CuO nanoparticles synthesized by pulsed laser ablation

Fast, selective and low-cost sensors for nitric oxide (NO) detection are highly desirable due to the harmful effects of this gas. Low temperature NO detection is challenging, requiring selective and effective catalytic processes. Here, we present an experimentally based CuO-NO interaction model in the 50–400 °C temperature range and a promising NO chemoresistive sensing device working at 50 °C based on CuO nanoparticles (NPs) produced by pulsed laser ablation in liquid environment (PLAL). Ligand-free Cu/Cu2O nanostructures produced by PLAL were converted into 35 ± 12 nm CuO NPs by 400 °C annealing, and analysed by X-Ray Diffraction, Scanning Electron Microscopy and Energy Dispersive X-ray techniques. The chemoresistive sensor is produced by drop-casting the CuO NPs suspension onto an interdigitated electrode and tested in a flow-controlled test chamber. Below 250 °C, oxidation behavior is recorded, while above 350 °C reduction takes place, with a peculiar transient regime observed at 300 °C. A full model of CuO-NO interaction is proposed, based on Langmuir adsorption theory and kinetics barriers extracted by response curves in the 50–400 °C temperature range. A peculiar catalytic activity of CuO NPs emerges in combination with oxygen species absorbed at different temperature, leading to effective NO detection. The ease and scalability of CuO NPs production by PLAL and the reported fast and selective NO sensor working at 50 °C open promising routes towards exploitation for massive and affordable harmful gas detection.