Chloride Sensor Research Articles

A smartphone-based chloridometer for point-of-care diagnostics of cystic fibrosis

Chloride in sweat is an important diagnostic marker for cystic fibrosis (CF), but the implementation of point-of-care systems for diagnosis is hindered by the prohibitive costs of existing chloride sensors. To enable low cost diagnostic solutions, we recently established a citrate-derived synthesis platform for the development of new fluorescence sensors with high selectivity for chloride. As a next step, we herein designed a smartphone operated chloridometer that optimizes the analytical performance of the citrate-derived sensor materials for the detection of chloride in sweat. The sensor material demonstrated a wide linear range of 0.8–200mM chloride and a diffusion-limited response time; sweat chloride levels corresponded to measurable changes in fluorescence emission that was captured by a smartphone. Clinical validation was performed with sweat from individuals with and without CF, demonstrating convenient sweat diagnostics with reliable detection of cystic fibrosis. To our knowledge, this is the first clinical study of a smartphone-based chloride sensor, paving the way for point-of-care diagnostic systems for CF.

On the origin of chloride-induced emission enhancement in ortho substituted squaramides

Abstract There is significant current interest in the development of fluorescent sensors for the physiologically relevant chloride ion. In this study we report a new squaramide-based chloride sensor, derived from ethyl ortho aminobenzoate, whose emission intensity increases by nearly 40% upon chloride binding. The intramolecularly hydrogen bonded squaramide exhibited a blue-shifted excitation spectrum relative to its absorption spectrum, and its emission displayed excitation wavelength dependence. These unusual characteristics were attributed to the existence of two ground state conformers for the unbound squaramide; an intramolecular hydrogen bonded conformer which undergoes non-radiative decay and a non-hydrogen bonded non-planar conformer from which emission occurs. Using computational investigations we identified two nearly degenerate excited states arising from two different charge transfer pathways with the squaramide nitrogen atom as the donor and either the cyclobutene dione ring or the ortho substituted N-phenyl ring functioning as acceptors. In the unbound squaramide, this competition between the two charge transfer pathways decreases fluorescence intensity. Chloride binding, suppresses charge transfer into the cyclobutene dione ring thereby enhancing emission intensity. Our study contributes to an increased understanding of the excited states of squaramides and could facilitate their use in the development of new sensors.

A wearable potentiometric sensor with integrated salt bridge for sweat chloride measurement

The development of wearable sensors to measure biomarkers in sweat remains a major technological challenge. Here we report on a wearable, potentiometric, thin film sweat chloride sensor. Potentiometric devices provide a relatively simple technology for sweat sensing, however, equilibration between the reference and test solutions is a significant source of error. We have developed a sweat chloride sensor with integrated salt bridge that minimizes equilibration and enables stable measurements over extended periods of time. The sensor shows a very small concentration drift even with small sample volumes. The measurement variation was less than 2mM at low chloride ion concentration (10mM) and 5mM at high concentration (150mM), spanning the range for healthy individuals and CF patients. Finally, in on-body tests we show that the sweat chloride concentration in healthy individuals is dependent on exercise intensity, indicating that the sensor has a potential for a fitness monitoring applications.

Sensing abilities of functionalized calix[4]arene coated QCM sensors towards volatile organic compounds in aqueous media

This study presents the sensing studies of QCM sensors which coated with calix[4]arene derivatives bearing different functional groups towards some selected Volatile Organic Compounds (VOCs). Initial experiments revealed that QCM sensor coated with calix-3 bearing bromopropyl functionalities was relatively more effective sensor for methylene chloride (MC) emissions than the other calix[4]arene coated QCM sensors, in aqueous media. In further experiments, this effective calix-3 coated QCM sensor were used in detailed sensing studies of selected VOCs. However, the results demonstrated that calix-3 coated QCM sensor was most useful sensor for toluene (TOL) emissions among all. Moreover, the sensing of TOLs with calix-3 coated QCM sensor was also evaluated in terms of sorption phenomena. Consequently, calix-3 coated QCM sensor was good sensor for TOL emissions, and thus it demonstrated that the coating of QCM sensor surface with calixarenes was good approach for sensing of the VOCs.

Embedded sensor system to detect chloride permeation in concrete: an overview

ABSTRACTExposure of concrete structures to chloride-bearing solutions such as sea water or de-icing salts brine can affect their durability to stand against deterioration caused by corrosion of steel reinforcement. In order to monitor the chloride ingress into concrete, embedded chloride sensors can be used in concrete structures. Through the sensors, they monitor the initiation of corrosion of steel reinforcement with time, and measure the open circuit potential and polarisation of steel reinforcement, humidity inside the concrete, chloride content and many more. This paper provides an overview of the latest development of chloride permeation measurement in concrete by evaluating the current techniques being used in industry and highlighting a new approach to monitor chloride ion progress in concrete structures wirelessly.

A noninvasive optical approach for assessing chloride extrusion activity of the K\u2013Cl cotransporter KCC2 in neuronal cells

BackgroundCation-chloride cotransporters (CCCs) are indispensable for maintaining chloride homeostasis in multiple cell types, but K–Cl cotransporter KCC2 is the only CCC member with an exclusively neuronal expression in mammals. KCC2 is critical for rendering fast hyperpolarizing responses of ionotropic γ-aminobutyric acid and glycine receptors in adult neurons, for neuronal migration in the developing central nervous system, and for the formation and maintenance of small dendritic protrusions—dendritic spines. Deficit in KCC2 expression and/or activity is associated with epilepsy and neuropathic pain, and effective strategies are required to search for novel drugs augmenting KCC2 function.ResultsWe revised current methods to develop a noninvasive optical approach for assessing KCC2 transport activity using a previously characterized genetically encoded chloride sensor. Our protocol directly assesses dynamics of KCC2-mediated chloride efflux and allows measuring genuine KCC2 activity with good spatial and temporal resolution. As a proof of concept, we used this approach to compare transport activities of the two known KCC2 splice isoforms, KCC2a and KCC2b, in mouse neuronal Neuro-2a cells.ConclusionsOur noninvasive optical protocol proved to be efficient for assessment of furosemide-sensitive chloride fluxes. Transport activities of the N-terminal splice isoforms KCC2a and KCC2b obtained by the novel approach matched to those reported previously using standard methods for measuring chloride fluxes.

Polarization Behaviour of Silver in Model Solutions

When studying chloride-induced corrosion in reinforced concrete structures, essential information of interest is the concentration of chloride ions in the system. The absence of a reliable method for monitoring the free chloride ions justifies the attempts towards establishing a feasible practice in the application of the already known Ag/AgCl electrode, as a chloride sensor. To identify the governing mechanism and cognition of causes for instability of the chloride sensors in highly alkaline medium (as concrete), it is necessary to study the polarization behaviour of silver in different aqueous solutions resembling the concrete environment. Following expectations and well-known fundamental background, the results from this work confirm that in the presence of chloride ions, silver chloride is the predominant reaction product, forming on the silver surface. Whereas, in the absence of chloride ions and/or presence of interfering ions, such as hydroxide ions, the oxidation process of AgCl formation is significantly dependent on the chloride concentration in the medium. Therefore, the formation of a stable AgCl layer on a Ag substrate (as would be required for sensors application for example) is a function of the presence and amount of interfering ions, together with the chloride concentration in the medium.

Citrate-based fluorescent materials for low-cost chloride sensing in the diagnosis of cystic fibrosis

Chloride is an essential electrolyte that maintains homeostasis within the body, where abnormal chloride levels in biological fluids may indicate various diseases such as Cystic Fibrosis. However, current analytical solutions for chloride detection fail to meet the clinical needs of both high performance and low material or labor costs, hindering translation into clinical settings. Here we present a new class of fluorescence chloride sensors derived from a facile citrate -based synthesis platform that utilize dynamic quenching mechanisms. Based on this low-cost platform, we demonstrate for the first time a selective sensing strategy that uses a single fluorophore to detect multiple halides simultaneously, promising both selectivity and automation to improve performance and reduce labor costs. We also demonstrate the clinical utility of citrate-based sensors as a new sweat chloride test method for the diagnosis of Cystic Fibrosis by performing analytical validation with sweat controls and clinical validation with sweat from individuals with or without Cystic Fibrosis. Lastly, molecular modeling studies reveal the structural mechanism behind chloride sensing, serving to expand this class of fluorescence sensors with improved chloride sensitivities. Thus citrate-based fluorescent materials may enable low-cost, automated multi-analysis systems for simpler, yet accurate, point-of-care diagnostics that can be readily translated into clinical settings. More broadly, a wide range of medical, industrial, and environmental applications can be achieved with such a facile synthesis platform, demonstrated in our citrate-based biodegradable polymers with intrinsic fluorescence sensing.

Wearable Potentiometric Chloride Sweat Sensor: The Critical Role of the Salt Bridge.

The components of sweat provide an array of potential biomarkers for health and disease. Sweat chloride is of interest as a biomarker for cystic fibrosis, electrolyte metabolism disorders, electrolyte balance, and electrolyte loss during exercise. Developing wearable sensors for biomarkers in sweat is a major technological challenge. Potentiometric sensors provide a relatively simple technology for on-body sweat chloride measurement, however, equilibration between reference and test solutions has limited the time over which accurate measurements can be made. Here, we report on a wearable potentiometric chloride sweat sensor. We performed parametric studies to show how the salt bridge geometry determines equilibration between the reference and test solutions. From these results, we show a sweat chloride sensor can be designed to provide accurate measurements over extended times. We then performed on-body tests on healthy subjects while exercising to establish the feasibility of using this technology as a wearable device.

The phospholipid flippase ATP8B1 mediates apical localization of the cystic fibrosis transmembrane regulator

Progressive familial intrahepatic cholestasis type 1 (PFIC1) is caused by mutations in the gene encoding the phospholipid flippase ATP8B1. Apart from severe cholestatic liver disease, many PFIC1 patients develop extrahepatic symptoms characteristic of cystic fibrosis (CF), such as pulmonary infection, sweat gland dysfunction and failure to thrive. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel essential for epithelial fluid transport. Previously it was shown that CFTR transcript levels were strongly reduced in livers of PFIC1 patients. Here we have investigated the hypothesis that ATP8B1 is important for proper CFTR expression and function.We analyzed CFTR expression in ATP8B1-depleted intestinal and pulmonary epithelial cell lines and assessed CFTR function by measuring short-circuit currents across transwell-grown ATP8B1-depleted intestinal T84 cells and by a genetically-encoded fluorescent chloride sensor. In addition, we studied CFTR surface expression upon induction of CFTR transcription.We show that CFTR protein levels are strongly reduced in the apical membrane of human ATP8B1-depleted intestinal and pulmonary epithelial cell lines, a phenotype that coincided with reduced CFTR activity. Apical membrane insertion upon induction of ectopically-expressed CFTR was strongly impaired in ATP8B1-depleted cells.We conclude that ATP8B1 is essential for correct apical localization of CFTR in human intestinal and pulmonary epithelial cells, and that impaired CFTR localization underlies some of the extrahepatic phenotypes observed in ATP8B1 deficiency.

HCl ppb-level detection based on QEPAS sensor using a low resonance frequency quartz tuning fork

In this report, a sensitive quartz-enhanced photoacoustic spectroscopy (QEPAS) based hydrogen chloride (HCl) sensor using a quartz tuning fork (QTF) with a resonance frequency of 30.72kHz was demonstrated for the first time. A fiber-coupled, continuous wave (CW), distributed feedback (DFB) diode laser emitting at 1.74μm was employed as the excitation laser source. Wavelength modulation spectroscopy and a 2nd harmonic detection technique were used to reduce the sensor background noise. An acoustic micro-resonator (mR) was added to the QTF sensor architecture to improve the signal amplitude. For the reported HCl sensor system operating at atmospheric pressure, a 550 ppbv (parts per billion by volume) minimum detection limit at 5739.27cm−1 was achieved when the modulation depth and the data acquisition time were set to 0.23cm−1 and 1s, respectively. The ppb-level detection sensitivity and robust design of the QEPAS technique makes it suitable for use in environmental monitoring and other applications.

Application of Distributed Wireless Chloride Sensors to Environmental Monitoring: Initial Results

Over the next 30 years, it is anticipated that the world will need to source 70% more food to provide for the growing population, and it is likely that a significant amount of this will have to come from irrigated land. However, the quality of irrigation water is also important, and measuring the quality of this water will allow management decisions to be made. Soil salinity is an important parameter in crop yield, and in this paper, we describe a chloride sensor system based on a low-cost robust screen-printed chloride ion sensor, suitable for use in distributed sensor networks. Previously, this sensor has been used in controlled laboratory-based experiments, but here we provide evidence that the sensor will find application outside of the laboratory in field deployments. We report on three experiments using this sensor; one with a soil column, one using a fluvarium, and finally on an experiment in a greenhouse. All these give an insight into the movement of chloride over small distances with high temporal resolution. These initial experiments illustrate that the new sensors are viable and usable with relatively simple electronics, and although subject to ongoing development, they are currently capable of providing new scientific data at high spatial and temporal resolutions. Therefore, we conclude that such chloride sensors, coupled with a distributed wireless network, offer a new paradigm in hydrological monitoring and will enable new applications, such as irrigation using mixtures of potable and brackish water, with significant cost and resource saving.

Sensitive and fast optical HCl gas sensor using a nanoporous fiber membrane consisting of poly(lactic acid) doped with tetraphenylporphyrin

A highly sensitive and fast sensor for gaseous hydrogen chloride (HCl) is described. It is based on the use of the optical probe 5,10,15,20-tetraphenylporphyrin contained in a poly(lactic acid) nanoporous fiber membrane that was fabricated via electrospinning. With its porous structure, the sensor overcomes the slow gas absorption and diffusion of other sensing materials. Field emission SEM was employed to characterize the morphology of the sensing membrane. The exposure to HCl gas causes a color change from pink to green that is due to the protonation of the central nitrogen atoms of the porphyrin, and fluorescence is quenched. The largest increase in absorbance occurs at 442 nm. HCl gas can be detected in this way even at sub-ppm levels. The detection limit is 34 ppb, and the response time is as short as 5 s. The sensor is highly stable after ten cycles of tracing HCl gas and recovery, and response is fully reversible.

Effect of electrochemical chloride extraction treatment on the corrosion of steel rebar in chloride contaminated mortar

Purpose This work aims to demonstrate the use of electrochemical chloride extraction (ECE) to remove chloride ions away from the steel rebar in chloride-contaminated mortar and to mitigate the corrosion of the embedded steel. Design/methodology/approach To simulate salt contamination in concrete, sodium chloride was added at 0.5 per cent by weight of cement in the fresh mortar featuring a water-to-cement ratio of 0.45. The ECE treatments were varied at two electrical current densities (1 and 5 A/m2), using two electrolytes (0.1M NaOH and 0.1M Na3BO3 solutions) and for two periods (2 and 4 weeks). The average free chloride concentration in cement mortars before and after ECE treatment was quantified using a customized chloride sensor, whereas the spatial distribution of relevant elements was obtained using energy-dispersive X-ray spectroscopy. The effect of ECE treatment on the electric resistivity of mortar and the corrosion resistance of steel rebar was investigated by electrochemical impedance spectroscopy and potentiodynamic polarization measurements, respectively. Findings The experimental results reveal that the ECE treatment was effective in removing chlorides and in improving electric resistivity and compressive strength of the mortar, when using the sodium borate solution as the electrolyte. In this case, a 4-week ECE treatment at 1 A/m2 decreased the free chloride content in the mortar by 70 per cent, significantly increased the Ca/Si ratio in the mortar near rebar, led to a more refined and less permeable microstructure of the mortar and significantly improved its compressive strength. The ECE treatment was able to halt the chloride-induced corrosion of steel rebar by passivation. A 4-week ECE treatment at 1 A/m2 using sodium hydroxide and sodium borate solutions decreased the corrosion rate of rebar by 36 and 34 per cent, respectively. Originality/value This electrochemical rehabilitation of steel-reinforced concrete under chloride-contaminated condition is very effective in prolonging its service life.

A DNA-based sensor for intracellular chloride

A DNA-based sensor for intracellular chloride

DNA nanotechnology: Measuring chloride in live cells.

A nucleic acid-based chloride sensor is used to image and quantify spatiotemporal chloride transport in the living cell.

Electrochemical sensor for mercuric chloride based on graphene-MnO2 composite as recognition element

In this paper, graphene and MnO2 nanoparticle were programmed to synthesize a nanocomposite, which was used to modified glassy carbon electrode (GCE). The presence of Gr-MnO2 nanocomposite has enhanced the electrochemical performance of the GCE towards the mercuric chloride (HgCl2). Electrochemical behaviors of HgCl2 on different electrodes were evaluated by cyclic voltammetry, the result shows that the Gr-MnO2 nanocomposite modified electrode showed higher chemical activity with HgCl2 than bare GCE, MnO2/GCE and Gr/GCE. In PBS solution (pH=5.5), the oxidation peak current raised as the concentration of HgCl2 increased from 12.1 to 210.8μM, the detection limit was 2.0μM (S/N=3). The modified electrode showed good selectivity, high stability and excellent regeneration.

A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.

Mammalian with-no-lysine [K] (WNK) kinases are a family of four serine-threonine protein kinases, WNK1-4. Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. Increased Na(+) reabsorption through Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule plays an important role in the pathogenesis of hypertension in patients with PHA2. However, how WNK1 and WNK4 regulate NCC and how mutations of WNKs cause activation of NCC have been controversial. Here, we review current state of literature supporting a compelling model that WNK1 and WNK4 both contribute to stimulation of NCC. The precise combined effects of WNK1 and WNK4 on NCC remain unclear but likely are positive rather than antagonistic. The recent discovery that WNK kinases may function as an intracellular chloride sensor adds a new dimension to the physiological role of WNK kinases. Intracellular chloride-dependent regulation of WNK's may underlie the mechanism of regulation of NCC by extracellular K(+). Definite answer yet will require future investigation by tubular perfusion in mice with altered WNK kinase expression.

An Un-Bleachable YFP-Based Chloride Sensor

Prestin (SLC26A5), the protein responsible for electromotility in the mammalian outer hair cell, remains incompletely characterized. We are interested in the protein's transporter/channel-like behavior. Clearly, the functional analysis of many chloride-related membrane proteins, such as channels/transporters/receptors, would benefit from a genetically encoded chloride sensor with reliable properties. Recently we developed an YFP-based chloride sensor, mCl-YFP (Sheng et al., PLoS ONE 2014, 9(6): e99095), with chloride Kd of 14 mM and pKa of 5.9, as well as 15-fold better photostability than wild-type EYFP. Using this chloride sensor, we demonstrated enhanced dynamic flux of chloride in the mM range into HEK cells expressing the fused protein of prestin and mCl-YFP. In order to avoid photobleaching interference during long exposure measurements, a new chloride sensor was developed with 80-fold better photostability than wild-type EYFP by stabilizing the chromophore structure via hydrogen-bond network. Other characteristics are similar to the original sensor we developed. We are currently testing the new sensor's sensitivity to other anions that typically exist in cells. We expect that this sensor will provide more detailed information on the transporter function of prestin, as well as other membrane proteins.

Monitoring the Electrochemical Response of Chloride Sensors Embedded in Cement Paste

ABSTRACTThis work presents the electrochemical behavior of Ag/AgCl electrodes (chloride sensors) in cement paste environment, monitored over a period of 180 days via open circuit potential (OCP) readings and electrochemical impedance spectroscopy (EIS). The EIS response indicates modification of the sensors’ morphology, in particular alteration of the AgCl layers, as a result of continuous chloride penetration into the bulk matrix towards the vicinity of the sensor/cement paste interface. A gradual shift to more cathodic OCP values and stabilization at approximately -1mVSCE to 2mVSCE was observed at the end of the test, reflecting chloride content of 820mM to 930mM in the pore solution surrounding the sensors, which differs 5-10% from the chloride concentration in the external solution. The water soluble chloride content in the cement pate, as destructively measured wet chemically by Volhard method and photometry, was in the range of 1100mM - 1300mM i.e. about 30-50% more than the chloride concentration in the external solution. This difference of maximum 50% in the recorded chloride levels is attributed to the fact that the sensors “read” the average amount of free chloride at the interface sensor/cement paste, while the destructively measured water soluble chloride reflects the average free (with possible contribution of physically bound chloride) in the total volume of analyzed cement paste. It can be concluded that for the conditions of this experiment, more reliable free chloride content is measured via the sensors’ readings. Hence, if chloride thresholds for corrosion initiation are to be determined, the sensors’ readings will be more representative and accurate if compared to destructive water soluble chloride determination.