Chloride Sensor Research Articles

WNK kinase is a vasoactive chloride sensor in endothelial cells

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, a prototypical vasodilator, stimulated a rapid reduction in intracellular Cl- concentration ([Cl-]i) due to the activation of TMEM16A, a Cl- channel, in ECs of resistance-size arteries. TMEM16A channel-mediated Cl- signaling activated WNK kinase, which phosphorylated its substrate proteins SPAK and OSR1 in ECs. OSR1 potentiated transient receptor potential vanilloid 4 (TRPV4) currents in a kinase-dependent manner and required a conserved binding motif located in the channel C terminus. Intracellular Ca2+ signaling was measured in four dimensions in ECs using a high-speed lightsheet microscope. WNK kinase-dependent activation of TRPV4 channels increased local intracellular Ca2+ signaling in ECs and produced vasodilation. In summary, we show that TMEM16A channel activation reduces [Cl-]i, which activates WNK kinase in ECs. WNK kinase phosphorylates OSR1 which then stimulates TRPV4 channels to produce vasodilation. Thus, TMEM16A channels regulate intracellular Cl- signaling and WNK kinase activity in ECs to control arterial contractility.

Embeddable Chloride Sensor for Monitoring Chloride Penetration into Cement Mortar.

A composite solid chloride sensor consisting of two single sensors, i.e., Ag/AgCl working electrode and Mn/MnO2 reference electrode, was developed. The Ag/AgCl electrode was prepared by the anodic polarization method, while the Mn/MnO2 reference electrode was prepared using the powder compaction technique. Then, the electrochemical performances such as stability, reproducibility, and sensitivity of the composite and single sensors were investigated in a saturated Ca(OH)2 solution and mortar specimen. A current density of 0.5 mA/cm2 and polarization time of 2.5 h were the optimal preparation parameters of the Ag/AgCl selective electrode. The Ag/AgCl selective electrode showed a linear potential response with the logarithm of chloride ion content in solution and had good stability, reproducibility, and anti-polarization performances. In addition, the Mn/MnO2 electrode exhibited potential stability after being activated in an alkaline solution for 60 days. The composite sensor demonstrated exceptional sensitivity to the Cl- content, boasting a slope of approximately 51.1 mV/decade, and showcased excellent stability in both solution and mortar specimens. In every measurement, the time needed for the potential of a composite sensor to become stable was less than 30 s. The sensor enables non-destructive in situ monitoring of the chloride ion content in cement mortar, thus realizing early warning of deterioration of reinforcement and guaranteeing long service life of the structure.

6-Methoxyquinoline immobilized nylon sensor for monitoring chloride concentration in reinforced concrete

An excess in the threshold concentration of chloride in concrete leads to the initiation of reinforcement corrosion, which in turn results in a reduction in the load-bearing capacity of reinforced concrete (RC) structures. Accordingly, the chloride concentration of RC is periodically investigated via a destructive method, but this process is time-consuming, labor-intensive, and costly. In order to overcome the limitations, this study sought to develop an optical chloride sensor that can be used in structural health monitoring. To this end, nylon was functionalized using formaldehyde and epichlorohydrine, after which 6-methoxy quinoline was covalently immobilized to manufacture a sensor. The developed sensor was found to be capable of measuring chloride concentrations (0–5,000 mM) and exhibited rapid responsiveness and reversibility. In addition, the developed sensor also showed a stable response even when exposed to the pH 13.4 environment for three months, and it could detect changes in chloride concentration even inside the mortar.

Hydrophilic redox buffers for textile-based potentiometric sensors

One of the barriers to the more widespread use of ion-selective electrodes (ISEs) in resource-limited areas is the need for frequent recalibration of such devices. The incorporation of a redox buffer to minimize the effect of redox-active impurities in the system has previously been shown to significantly improve reproducibility. To date, however, there have been no examples of redox buffers compatible with anion-sensing polymeric sensing membranes that can be incorporated into the inner filling solution of an ISE. Here, we introduce a novel hydrophilic redox buffer, cobalt(II/III) bis(terpyridine), and show the improvement of the standard deviation of E0 of chloride sensors from 2.7 to 0.3 mV upon introduction of the redox buffer into the inner filing solution of conventional, rod-shaped electrodes. The redox buffer is also compatible with a textile-based sensing platform, which was shown by incorporation into a textile-based platform with embedded ion-sensing and reference membranes. As only a surprisingly small number of hydrophilic redox buffers have been reported in the literature, the cobalt(II/III) bis(terpyridine) redox buffer may also find applications outside of the field of ISEs.

Wearable sweat chloride sensors: materials, fabrication and their applications.

Chloride is a crucial anion required for multiple functions in the human body including maintaining acid-base balance, fluid balance, electrical neutrality and supporting muscles and nerve cells. Low-chloride levels can cause nausea, diarrhoea, etc. Chloride levels are measured in different body fluids such as urine, serum, sweat and saliva. Sweat chloride measurements are used for multiple applications including disease diagnosis, sports monitoring, and geriatric care. For instance, a sweat chloride test is performed for cystic fibrosis screening. Further, sweat also offers continuous non-invasive access to body fluids for real-time monitoring of chloride that could be used for sports and geriatric care. This review focuses on wearable chloride sensors that are used for periodic and continuous chloride monitoring. The multiple sections in the paper discuss the clinical significance of chloride, detection methods, sensor fabrication methods and their application in cystic fibrosis screening, sports and geriatric care. Finally, the last section discusses the limitation of current sensors and future directions for wearable chloride sensors.

The proton channel OTOP1 is a sensor for the taste of ammonium chloride

Ammonium (NH4+), a breakdown product of amino acids that can be toxic at high levels, is detected by taste systems of organisms ranging from C. elegans to humans and has been used for decades in vertebrate taste research. Here we report that OTOP1, a proton-selective ion channel expressed in sour (Type III) taste receptor cells (TRCs), functions as sensor for ammonium chloride (NH4Cl). Extracellular NH4Cl evoked large dose-dependent inward currents in HEK-293 cells expressing murine OTOP1 (mOTOP1), human OTOP1 and other species variants of OTOP1, that correlated with its ability to alkalinize the cell cytosol. Mutation of a conserved intracellular arginine residue (R292) in the mOTOP1 tm 6-tm 7 linker specifically decreased responses to NH4Cl relative to acid stimuli. Taste responses to NH4Cl measured from isolated Type III TRCs, or gustatory nerves were strongly attenuated or eliminated in an Otop1−/− mouse strain. Behavioral aversion of mice to NH4Cl, reduced in Skn-1a−/− mice lacking Type II TRCs, was entirely abolished in a double knockout with Otop1. These data together reveal an unexpected role for the proton channel OTOP1 in mediating a major component of the taste of NH4Cl and a previously undescribed channel activation mechanism.

A Simple Fabrication Method of Chloride Sensor Based on Hot-Dipped Ag/AgCl@PVC for Water Quality Monitoring

A Simple Fabrication Method of Chloride Sensor Based on Hot-Dipped Ag/AgCl@PVC for Water Quality Monitoring

Hybrid cement composite-based sensor for in-situ chloride monitoring in concrete structures

In this paper, we present a rugged cementitious composite sensor for monitoring chloride ingress in concrete structures. The sensor is in the form of an electrochemical double-layer, consisting of a chloride ion-selective functionalized graphene film sandwiched between two cementitious composites. The cementitious composite chloride sensor was subjected to different chlorides concentrations and electrochemical impedance spectroscopy (EIS) measurements were conducted to characterize its response. The effect of the pore solution and the independent impact of temperature and humidity on the sensor’s response were also quantified. The experimental results showed that the sensor successfully measured chlorides concentration changes with good sensitivity. The sensor’s response was not affected by temperature and humidity and showed good reversibility and stability. However, the pH of the pore solution affected the sensor’s response to chlorides and a sensor calibration equation that considers pH is proposed. The characterization work presented herein provides a base for the development of such chloride sensing method, which can provide useful information for chloride diffusion models updating and health monitoring of the concrete structures subjected to sodium chloride.

Electrochemical Sensing of Urinary Chloride Ion Concentration for Near Real-Time Monitoring.

Urinary chloride concentration is a valuable health metric that can aid in the early detection of serious conditions, such as acid base disorders, acute heart failure, and incidences of acute renal failure in the intensive care unit. Physiologically, urinary chloride levels frequently change and are difficult to measure, involving time-consuming and inconvenient lab testing. Thus, near real-time simple sensors are needed to quickly provide actionable data to inform diagnostic and treatment decisions that affect health outcomes. Here, we introduce a chronopotentiometric sensor that utilizes commercially available screen-printed electrodes to accurately quantify clinically relevant chloride concentrations (5-250 mM) in seconds, with no added reagents or electrode surface modification. Initially, the sensor's performance was optimized through the proper selection of current density at a specific chloride concentration, using electrical response data in conjunction with scanning electron microscopy. We developed a unique swept current density algorithm to resolve the entire clinically relevant chloride concentration range, and the chloride sensors can be reliably reused for chloride concentrations less than 50 mM. Lastly, we explored the impact of pH, temperature, conductivity, and additional ions (i.e., artificial urine) on the sensor signal, in order to determine sensor feasibility in complex biological samples. This study provides a path for further development of a portable, near real-time sensor for the quantification of urinary chloride.

Control of sodium and potassium homeostasis by renal distal convoluted tubules.

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Fluorescent copolymer aggregate sensor for lithium chloride.

We report a copolymeric fluorescent sensor that is selective for lithium chloride. The two constituent polymers comprise pendent triphenylethylene (TPE) moieties for aggregate induced emission (AIE) along with either strapped-calix[4]pyrrole or secondary ammonium groups that drive aggregation via self-assembly upon polymer mixing. Addition of LiCl in acetonitrile disrupts the strapped-calix[4]pyrrole/secondary ammonium chloride salt host-guest crosslinks leading to disaggregation of the polymer chains and a decrease in TPE emission. The lack of AIE perturbation upon addition of NaCl, KCl, MgCl2 or CaCl2 provides for high selectivity for LiCl relative to potential interferants. This supramolecular dual polymer approach could serve as a complement to more traditional sensor systems.

Photonic crystal nanostructure as a photodetector for NaCl solution monitoring: theoretical approach.

In this research, we have a theoretical simple and highly sensitive sodium chloride (NaCl) sensor based on the excitation of Tamm plasmon resonance through a one-dimensional photonic crystal structure. The configuration of the proposed design was, [prism/gold (Au)/water cavity/silicon (Si)/calcium fluoride (CaF2)10/glass substrate]. The estimations are mainly investigated based on both the optical properties of the constituent materials and the transfer matrix method as well. The suggested sensor is designed for monitoring the salinity of water by detecting the concentration of NaCl solution through near-infrared (IR) wavelengths. The reflectance numerical analysis showed the Tamm plasmon resonance. As the water cavity is filled with NaCl of concentrations ranging from 0 g l-1 to 60 g l-1, Tamm resonance is shifted towards longer wavelengths. Furthermore, the suggested sensor provides a relatively high performance compared to its photonic crystal counterparts and photonic crystal fiber designs. Meanwhile, the sensitivity and detection limit of the suggested sensor could reach the values of 24 700 nm per RIU (0.576 nm (g l)-1) and 0.217 g l-1, respectively. Therefore, the suggested design could be of interest as a promising platform for sensing and monitoring NaCl concentrations and water salinity as well.

A non-dispersive infrared sensor for real-time detection of cyanogen chloride

Cyanogen chloride, as a systemic toxic agent, can cause death rapidly. In this paper, a non-dispersive infrared sensor was designed for the infrared absorption detection of cyanogen chloride at 800 cm-1. The roughness of the internal coating material was analyzed by experiments, and the gold-plated gas chamber was selected. The light path propagation of different cross-section gas chambers was simulated, and the circular section gas chamber was selected to increase the infrared detector signal. The effect of flow rate on voltage was studied. The standard curve between voltage and concentration was obtained under the optimal condition of 0.4 L min-1. The maximum response time was 19 s, and RSD was less than 2%. The interference experiment results showed that common gases entering the gas chamber do not cause interference. The non-dispersive infrared sensor for cyanogen chloride has good stability and detects cyanogen chloride in real-time.

Using SuperClomeleon to measure changes in intracellular chloride during development and after early life stress.

Intraneuronal chloride concentrations ([Cl-]i) decrease during development resulting in a shift from depolarizing to hyperpolarizing γ-aminobutyric acid (GABA) responses via chloride-permeable GABAA receptors. This GABA shift plays a pivotal role in postnatal brain development, and can be strongly influenced by early life experience. Here, we assessed the applicability of the recently developed fluorescent SuperClomeleon (SClm) sensor to examine changes in [Cl-]i using two-photon microscopy in brain slices. We used SClm mice of both sexes to monitor the developmental decrease in neuronal chloride levels in organotypic hippocampal cultures. We could discern a clear reduction in [Cl-]i between DIV3 and DIV9 (equivalent to the second postnatal week in vivo) and a further decrease in some cells until DIV22. In addition, we assessed alterations in [Cl-]i in the medial prefrontal cortex (mPFC) of P9 male SClm mouse pups after early life stress (ELS). ELS was induced by limiting nesting material between P2 and P9. ELS induced a shift towards higher (i.e. immature) chloride levels in layer 2/3 cells in the mPFC. Although conversion from SClm fluorescence to absolute chloride concentrations proved difficult, our study underscores that the SClm sensor is a powerful tool to measure physiological changes in [Cl-]i in brain slices.Significance StatementThe reduction of intraneuronal chloride concentrations is crucial for brain development, as it ensures a shift from the initial excitatory action of the neurotransmitter GABA in immature neurons to the inhibitory GABA signaling in the adult brain. Despite the significance of chloride maturation, it has been difficult to study this phenomenon in experiments. Recent development of chloride sensors enable direct imaging of intracellular chloride signaling in neurons. Here we assessed the applicability of the SuperClomeleon chloride sensor to measure physiologically relevant changes in chloride levels using two-photon microscopy in cultured and acute brain slices. Although we also point out some limitations, we conclude that the SuperClomeleon sensor is a powerful tool to measure physiological changes in intracellular chloride.

Green and Integrated Wearable Electrochemical Sensor for Chloride Detection in Sweat.

Wearable sensors for sweat biomarkers can provide facile analyte capability and monitoring for several diseases. In this work, a green wearable sensor for sweat absorption and chloride sensing is presented. In order to produce a sustainable device, polylactic acid (PLA) was used for both the substrate and the sweat absorption pad fabrication. The sensor material for chloride detection consisted of silver-based reference, working, and counter electrodes obtained from upcycled compact discs. The PLA substrates were prepared by thermal bonding of PLA sheets obtained via a flat die extruder, prototyped in single functional layers via CO2 laser cutting, and bonded via hot-press. The effect of cold plasma treatment on the transparency and bonding strength of PLA sheets was investigated. The PLA membrane, to act as a sweat absorption pad, was directly deposited onto the membrane holder layer by means of an electrolyte-assisted electrospinning technique. The membrane adhesion capacity was investigated by indentation tests in both dry and wet modes. The integrated device made of PLA and silver-based electrodes was used to quantify chloride ions. The calibration tests revealed that the proposed sensor platform could quantify chloride ions in a sensitive and reproducible way. The chloride ions were also quantified in a real sweat sample collected from a healthy volunteer. Therefore, we demonstrated the feasibility of a green and integrated sweat sensor that can be applied directly on human skin to quantify chloride ions.

The Effect of Paper on the Detection Limit of Paper-Based Potentiometric Chloride Sensors.

While paper is an excellent material for use in many other portable sensors, potentiometric paper-based sensors have been reported to perform worse than conventional rod-shaped electrodes, in particular in view of limits of detection (LODs). Reported here is an in-depth study of the lower LOD for Cl- measurements with paper-based devices comprising AgCl/Ag transducers. Contamination by Cl- from two commonly used device materials─a AgCl/Ag ink and so-called ashless filter paper─was found to increase the concentration of Cl- in paper-contained samples far above what is expected for the spontaneous dissolution of the transducer's AgCl, thereby worsening lower LODs. In addition, for the case of Ag+, the commonly hypothesized adsorption of metal cations onto filter paper was found not to significantly affect the performance of AgCl/Ag transducers. We note that in the context of chemical analysis, metal impurities of paper are often mentioned in the literature, but Cl- contamination of paper has been overlooked.

All-solid-state chloride sensor for in-situ monitoring of chloride penetration in concrete

In this study, an all-solid-state chloride sensor constituted with Ag/AgCl working electrode and Mn/MnO2 reference electrode was developed. The Ag/AgCl electrode fabricated with galvanostatic anodization method and Mn/MnO2 fabricated with powder compaction method exhibited homogeneous micro-structures. The as-prepared chloride sensor showed good ability of polarization resistance, long-term stability, perfect Nernst response, and low hysteresis effect in solutions. The influence of pH, temperature, and interfering ions on the chloride response of the sensor was also systematically investigated. Furthermore, the chloride sensor was embedded in the mortar specimen and used to monitor the chloride penetration process during the capillary absorption test. The results indicate that the chloride sensor can provide accurate chloride content variations of the mortar specimens, and it has great potential for non-destructively monitoring the chloride penetration in concrete structures.

Tetraphenylethylene sulfonate derivative as turn-on fluorescent sensor for berberine chloride detection in aqueous solution

A negatively-charged tetraphenylethylene derivative (TPE-SE) was designed and synthesized as turn-on fluorescent sensor for berberine chloride (BBC) detection in aqueous solution. The fluorescent property and detection mechanism were elucidated by UV–vis absorption spectra, photoluminescence spectra, dynamic light scattering experiments. The results reveal that the BBC can lead to aggregation-induced emission of TPE-SE due to the electrostatic interactions, endowing TPE-SE with excellent turn-on detecting ability, high selectivity and sensitivity to BBC. The detection limit is as low as 6.58 × 10−6M. These results should be applicable to fabricate special turn-on fluorescent sensors towards various antibiotics, and it is crucially important for achieving reasonable control and intake of small biomolecules.

Turn-on fluorescent sensor for berberine chloride in aqueous solution based on dicyanodistyrylbenzene derivative

A novel fluorescent probe based on water-soluble dicyanodistyrylbenzene derivative (DCS-SE) has been prepared for berberine chloride (BBC) detection. The sensing performance and mechanism of DCS-SE were elucidated by photoluminescence spectra and scanning electron microscopy techniques. The experimental results reveal that DCS-SE possesses high selectivity, fast response and quantitative recognition towards BBC in aqueous solution. Moreover, due to the electrostatic interactions induced aggregation and the subsequent aggregation-induced emission effect, DCS-SE exhibits special turn-on detecting ability, with detection limit as low as 9.3 × 10−8 M. The strategy and principle outlined in this work may be applicable to design and prepare turn-on fluorescent sensors towards various antibiotic and biomolecules.

Effect of chloride penetration on electrical resistivity of CNT–CF/cement composites and its application as chloride sensor for reinforced mortar

This study was conducted to investigate the effect of chloride (Cl) penetration on the resistivity of highly conductive composites containing carbon nanotubes (CNTs) and carbon fibers (CFs). First, Cl ions were penetrated into the hardened composite specimens with the application of an electrical charge, and the profiles of the Cl contents, conductivity, hydration, and pore structures were then evaluated. Second, the composite sensors were embedded in a reinforced mortar and immersed in a NaCl solution. Third, the ion distribution in the composite sensor immersed in the NaCl solution was visualized via element mapping using a scanning electron microscopy–energy-dispersive X-ray analysis and an electron probe micro-analyzer. It was found that the resistivity of the composites increased as the Cl penetrated the specimens, and this phenomenon was presumably due to the clogging of the CNT network. The results indicated that the Cl penetration could be monitored by checking the trend of change in the resistance value of multiple sensors over time (trend analysis), and not just by measuring the instantaneous resistance value of a single sensor (deterministic measurement).