dynamic-electrochemical-measurement-of-chloride-ions

Dynamic Electrochemical Measurement of Chloride Ions

This protocol describes the dynamic measurement of chloride ions using the transition time of a silver silver chloride (Ag/AgCl) electrode. Silver silver ...

University of Twente

In this tutorial review the use of stimulus-sensitive hydrogels as sensors and actuators for (micro)analytical applications is discussed. The first part of the article is aimed at making the reader familiar with stimulus-sensitive hydrogels, their chemical composition and their chemo-physical behavior. The prior art in the field, that comprises a number of sensors ranging from metal ion-sensitive sensors to antigen-sensitive sensors and a few actuators, is also treated in this part. The second part of the article focusses on the use of stimulus-sensitive hydrogels for microsensors and microactuators as well as their application in micro total analysis systems. The benefits of stimulus-sensitive hydrogels, their miniaturisation and the use of 365 nm UV-photolithography as a fast economical manufacturing technique are discussed.

Stimulus-sensitive hydrogels and their applications in chemical (micro)analysis.

The optimization process of a planar interdigitated conductivity detector for measuring very low electrolyte concentrations for use in a lab-on-chip gas detection system is described. An electrical equivalent of the sensor is given, which includes the double layer capacitance dependency on the electrolyte concentration, resulting in a better description of the impedance of the sensor. The cell constant of the sensor is minimized to reduce the cell resistance in low specific conductivity solutions under the restriction of a small electrode area (> or = 0.1 cm(2)) for fast measurement, prescribed by the ammonia detection system. The small size makes it suitable for integration in micro channels. The developed sensor has a cell constant of 7.9 m(-1) resulting in a maximum resistance for deionized water of 177 k Omega at a frequency of 1 kHz.

Optimization of an electrolyte conductivity detector for measuring low ion concentrations.

The development of a gas sampler for a miniaturized ambient ammonia detector is described. A micromachined channel system is realized in glass and silicon using powder blasting and anodic bonding. The analyte gas is directly mixed with purified water, dissolving the ammonia that will dissociate into ammonium ions. Carrier gas bubbles are subsequently removed from the liquid stream through a venting hole sealed with a microporous water repellent PTFE membrane. A flow restrictor is placed at the outlet of the sampler to create a small overpressure underneath the membrane, enabling the gas to leave through the membrane. Experiments with a gas flow of 1 ml min(-1), containing ammonia concentrations ranging from 9.4 ppm to 0.6 ppm in a nitrogen carrier flow have been carried out, at a water flow of 20 microl min(-1). The ammonium concentration in the sample solution is measured with an electrolyte conductivity detector. The measured values correspond with the concentration calculated from the initial ammonia concentration in the analyte gas, the fifty times concentration enhancement due to the gas-liquid volume difference and the theoretical dissociation equilibrium as a function of the resulting pH.

Sampling small volumes of ambient ammonia using a miniaturized gas sampler.

The so-called address-flow principle is described: a valveless, electroosmotically driven technology used for controlling the stream profile in a laminar flow chamber. The method is explained, and a theoretical description and experimental verification are presented. Adjustment of the flow of two electroosmotically controlled guiding streams, running parallel to a central sample stream, can be used for positioning the sample stream in the dimension perpendicular to the flow direction. The results presented show that address-flow microfluidics allow easy and accurate control of sample stream position and width. The electroosmotic flow (EOF)-controlled guiding of microfluidic flows described in this paper, is a new unit operation that might aid in separation and collection in microfluidic devices. One possible application of address-flow microfluidics is guiding of capillary electrophoresis-separated components over a multisensor array, in order to perform affinity assays.

Electroosmotic guiding of sample flows in a laminar flow chamber.

In this article a new method for the photolithographical deposition of temperature-sensitive hydrogels is presented. The method can be used in conjunction with standard 365 nm UV-photolithography to accurately dimension and position temperature-sensitive hydrogel microactuators in a highly parallel fashion. A number of characteristics of the hydrogels were investigated. These include: the photolithographical reproduction quality, the effect of the crosslinking density in the hydrogels on their swelling behavior, the swelling hysteresis behavior, the effect of dimensional constraints on the swelling of the hydrogels and the effect of copolymerization with an ionizable comonomer on the temperature behavior of the hydrogels. The method presents a considerable improvement in the microfabrication of temperature-sensitive hydrogel microactuators and has potential for the mass-fabrication of these interesting microactuators.

An efficient method for the fabrication of temperature-sensitive hydrogel microactuators.

The determination of inorganic cations in blood plasma is demonstrated using a combination of moving boundary electrophoresis (MBE) and zone electrophoresis. The sample loading performed under MBE conditions is studied with the focus on the quantitative analysis of lithium. A concentration adjustment takes place when the sample components migrate into the chip during the sample loading step. Using a heart-cutting method, a diluted sample plug is subsequently separated with capillary zone electrophoresis. The excessive dispersion that is typical of the samples with a high ionic strength is thereby prevented. The method can be easily applied to commercially available capillary electrophoresis microchips under the condition that the electroosmotic flow is suppressed. For the first time the lithium concentration is determined in the blood plasma from a patient on lithium therapy without sample pretreatment. Using a microchip with conductivity detection, a detection limit of 0.1 mmol/L is obtained for lithium in a 140 mmol/L sodium matrix.

Microchip analysis of lithium in blood using moving boundary electrophoresis and zone electrophoresis.

Herein, the influence of silicon surface modification via Si-C(n)H(2n+1) (n=10,12,16,22) monolayer-based devices on p-type 100 and n-type 100 silicon is studied by forming MIS (metal-insulator-semiconductor) diodes using a mercury probe. From current density-voltage (J-V) and capacitance-voltage (C-V) measurements, the relevant parameters describing the electrical behavior of these diodes are derived, such as the diode ideality factor, the effective barrier height, the flatband voltage, the barrier height, the monolayer dielectric constant, the tunneling attenuation factor, and the fixed charge density (Nf). It is shown that the J-V behavior of our MIS structures could be precisely tuned via the monolayer thickness. The use of n-type silicon resulted in lower diode ideality factors as compared to p-type silicon. A similar flatband voltage, independent of monolayer thickness, was found, indicating similar properties for all silicon-monolayer interfaces. An exception was the C10-based monolayer device on p-type silicon. Furthermore, low values of N(f) were found for monolayers on p-type silicon (approximately 6 x 10(11) cm(-2)). These results suggest that Si--C linked monolayers on flat silicon may be a viable material for future electronic devices.

Si-C linked organic monolayers on crystalline silicon surfaces as alternative gate insulators.

Rapid quantitative microchip capillary electrophoresis (CE) for online monitoring of drinking water enabling inorganic ion separation in less than 15 s is presented. Comparing cationic and anionic standards at different concentrations the analysis of cationic species resulted in non-linear calibration curves. We interpret this effect as a variation in the volume of the injected sample plug caused by changes of the electroosmotic flow (EOF) due to the strong interaction of bivalent cations with the glass surface. This explanation is supported by the observation of severe peak tailing. Conducting microchip CE analysis in a glass microchannel, optimized conditions are received for the cationic species K+, Na+, Ca2+, Mg2+ using a background electrolyte consisting of 30 mmol/L histidine and 2-(N-morpholino)ethanesulfonic acid, containing 0.5 mmol/L potassium chloride to reduce surface interaction and 4 mmol/L tartaric acid as a complexing agent resulting in a pH-value of 5.8. Applying reversed EOF co-migration for the anionic species Cl-, SO42- and HCO3- optimized separation occurs in a background electrolyte consisting of 10 mmol/L 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) and 10 mmol/L HEPES sodium salt, containing 0.05 mmol/L CTAB (cetyltrimethylammonium bromide) resulting in a pH-value of 7.5. The detection limits are 20 micromol/L for the monovalent cationic and anionic species and 10 micromol/L for the divalent species. These values make the method very suitable for many applications including the analysis of abundant ions in tap water as demonstrated in this paper.

Rapid inorganic ion analysis using quantitative microchip capillary electrophoresis.

The electrochemical behavior of Si--C linked organic monolayers is studied in electrolyte-insulator-Si devices, under conditions normally encountered in potentiometric biosensors, to gain fundamental knowledge on the behavior of such Si electrodes under practical conditions. This is done via titration experiments, Mott-Schottky data analysis, and data fitting using a site-binding model. The results are compared with those of native SiO(2) layers and native SiO(2) layers modified with hexamethyldisilazane. All samples display pH sensitivity. The number of Si--OH groups on the alkylated samples is calculated to be less than 0.7 % of that of a pure SiO(2) insulator, which still causes a pH sensitivity of approximately 25 mV per pH unit in the pH range: 4-7. The alkylated samples hardly suffer from response changes during up- and down-going titrations, which indicates that very little oxide is additionally formed during the measurements. The pK(a) values of all samples with monolayers (4.0-4.4) are lower than that of native SiO(2) (6.0). The long-term drift (of approximately 1 mV h(-1)) is moderate. The results indicate that biosensors composed of alkylated Si substrates are feasible if a cross-sensitivity towards pH in the sensor signal is taken into account.

pH sensitivity of Si--C linked organic monolayers on crystalline silicon surfaces.

Gastrointestinal ischemia is always accompanied by an increased luminal CO(2). Currently, air tonometry is used to measure luminal CO(2). To improve the response time a new sensor was developed, enabling continuous CO(2) measurement. It consists of a pH-sensitive hydrogel which swells and shrinks in response to luminal CO(2), which is measured by the pressure sensor. We evaluated the potential clinical value of the sensor during an in vitro and in vivo study.

Assessment of a new prototype hydrogel CO( 2 ) sensor; comparison with air tonometry.

In this work, we present a chip-integrated amperometric sensor targeted at the detection of hydrogen peroxide (H₂O₂) in the gaseous phase. Electrode chips are manufactured in a series of microfabrication steps and characterized electrochemically. Using such devices detection of H₂O₂ in an aqueous phase is shown by means of cyclic voltammetry and amperometry. Furthermore, it is discussed that variation of conditions such as the composition of the supporting electrolyte largely influences the obtained electrochemical signal. Additionally, electrochemical pretreatment of platinum working electrodes aiming at surface oxidation improves the limit of detection of the sensor and the linearity of the calibration curve at low H₂O₂ concentrations (<10 μM). Agarose-coated electrode chips are used for the measurement of H₂O₂ in the gaseous phase. Detection of H₂O₂ is shown in a static and in a flow-through setup. We find a limit of detection of approximately 42 ppb. Current work focuses on expanding the presented device to detection of H₂O₂ in exhaled breath condensate.

Developing an amperometric hydrogen peroxide sensor for an exhaled breath analysis system.

This paper reports a novel design of a miniaturized three-electrode electrochemical cell, the purpose of which is aimed at generating drug metabolites with a high conversion efficiency. The working electrode and the counter electrode are placed in two separate channels to isolate the reaction products generated at both electrodes. The novel design includes connecting channels between these two electrode channels to provide a uniform distribution of the current density over the entire working electrode. In addition, the effect of ohmic drop is decreased. Moreover, two flow resistors are included to ensure an equal flow of analyte through both electrode channels. Total conversion of fast reacting ions is achieved at flow rates up to at least 8 μL/min, while the internal chip volume is only 175 nL. Using this electrochemical chip, the metabolism of mitoxantrone is studied by microchip electrospray ionization-mass spectrometry. At an oxidation potential of 700 mV, all known metabolites from direct oxidation are observed. The electrochemical chip performs equally well, compared to a commercially available cell, but at a 30-fold lower flow of reagents.

Improved conversion rates in drug screening applications using miniaturized electrochemical cells with frit channels.

Many research efforts over the last few decades have been devoted to sensing lactate as an important analytical target in clinical care, sport medicine, and food processing. Therefore, research in designing lactate sensors is no longer in its infancy and now is more directed toward viable sensors for direct applications. In this review, we provide an overview of the most immediate and relevant developments toward this end, and we discuss and assess common transduction approaches. Further, we critically describe the pros and cons of current commercial lactate sensors and envision how future sensing design may benefit from emerging new technologies.

Lactate biosensors: current status and outlook.

Ion selective electrodes (ISE) are used extensively for the potentiometric determination of ion concentrations in electrolytes. However, the inherent drift in these measurements and the requirement of a stable reference electrode restrict the feasibility of this method for long-term in-situ applications. This work presents a chronopotentiometric approach to minimize drift and avoid the use of a conventional reference electrode for measuring chloride ion concentration. An anodic current pulse is applied to a Ag/AgCl working electrode which initiates a faradaic reaction that depletes the chloride ions near the electrode surface. The rate of change in potential at the Ag/AgCl electrode, due to chloride ion depletion, reaches an inflection point once the chloride ions deplete completely near the electrode surface. The moment of the inflection point, also known as the transition time, is a function of the chloride ion concentration and is described by the Sand equation. It is shown that the square root of the transition time is linearly proportional to the chloride ion concentration. Drift in the response over two weeks is negligible: 59 μM/day when measuring 1 mM of Cl(-) ions using a 10 A m(-2) current pulse. The transition time at a specific ion concentration can be tuned by the applied current pulse, e.g., in a solution containing 5 mM chloride ions, the transition times with current pulses of 10 and 20 A m(-2) are 1.56 and 0.25s, respectively. The moment of inflection determines the response, and thus is independent of the absolute potential of reference electrode. Therefore, any metal wire can act as a pseudo-reference electrode, enabling this approach for long-term and integrated-sensor applications such as measurement inside concrete structures.

No more conventional reference electrode: transition time for determining chloride ion concentration.

The costs of drug development have been rising exponentially over the last six decades, making it essential to select drug candidates in the early drug discovery phases before proceeding to expensive clinical trials. Here, we present novel screening methods using an electrochemical chip coupled online to mass spectrometry (MS) or liquid chromatography (LC) and MS, to generate phase I and phase II drug metabolites and to demonstrate protein modification by reactive metabolites. The short transit time (∼4.5 s) between electrochemical oxidation and mass spectrometric detection, enabled by an integrated electrospray emitter, allows us to detect a short-lived radical metabolite of chlorpromazine which is too unstable to be detected using established test routines. In addition, a fast way to screen candidate drugs is established by recording real-time mass voltammograms, which allows one to identify the drug metabolites that are expected to be formed upon oxidation by applying a linear potential sweep and simultaneously detect oxidation products. Furthermore, detoxification of electrochemically generated reactive metabolites of paracetamol was mimicked by their adduct formation with the antioxidant glutathione. Finally, the potential toxicity of reactive metabolites can be investigated by the modification of proteins, which was demonstrated by modification of carbonic anhydrase I with electrochemically generated reactive metabolites of paracetamol. With this series of experiments, we demonstrate the potential of this electrochemical chip as a complementary tool for a variety of drug metabolism studies in the early stages of drug discovery.

Mass spectrometric detection of short-lived drug metabolites generated in an electrochemical microfluidic chip.

Chloride is a crucial anion for various analytical applications from biological to environmental applications. In order to measure the chloride ion concentration, a measurement system is needed which can detect this concentration for prolonged times reliably. Chronopotentiometry is a technique which does not need a long term stable reference electrode and is therefore very suitable for prolonged ion concentration measurements. As the used electrode might be fouled by reaction products, this work focuses on a chronopotentiometric approach with a separated sensing electrode (sensor) and actuating electrode (actuator). Both actuation and sensor electrode are made of Ag/AgCl. A constant current is applied to the actuator and will start the reaction between Ag and Cl-, while the resulting Cl- ion concentration change is observed through the sensor, which is placed close to the actuator. The time it takes to locally deplete the Cl- ions is called transition time. Experiments were performed to verify the feasibility of this approach. The performed experiments show that the sensor detects the local concentration changes resulting from the current applied to the actuator. A linear relation between the Cl- ion concentration and the square root of the transition time was observed, just as was predicted by theory. The calibration curves for different chips showed that both a larger sensor and a larger distance between sensor and actuator resulted in a larger time delay between the transition time detected at the actuator and the sensor.

Article	Year
Stimulus-sensitive hydrogels and their applications in chemical (micro)analysis. The Analyst\| PubMed ID: 12741636	2003
Optimization of an electrolyte conductivity detector for measuring low ion concentrations. Lab on a chip\| PubMed ID: 15100845	2002
Sampling small volumes of ambient ammonia using a miniaturized gas sampler. Lab on a chip\| PubMed ID: 15159787	2004
Electroosmotic guiding of sample flows in a laminar flow chamber. Electrophoresis\| PubMed ID: 15565693	2004
An efficient method for the fabrication of temperature-sensitive hydrogel microactuators. Lab on a chip\| PubMed ID: 15570375	2004
Microchip analysis of lithium in blood using moving boundary electrophoresis and zone electrophoresis. Electrophoresis\| PubMed ID: 16078197	2005
Si-C linked organic monolayers on crystalline silicon surfaces as alternative gate insulators. Chemphyschem : a European journal of chemical physics and physical chemistry\| PubMed ID: 16208740	2005
Rapid inorganic ion analysis using quantitative microchip capillary electrophoresis. Journal of chromatography. A\| PubMed ID: 16310794	2006
pH sensitivity of Si--C linked organic monolayers on crystalline silicon surfaces. Chemphyschem : a European journal of chemical physics and physical chemistry\| PubMed ID: 17121410	2007
Assessment of a new prototype hydrogel CO( 2 ) sensor; comparison with air tonometry. Journal of clinical monitoring and computing\| PubMed ID: 17180731	2007
Developing an amperometric hydrogen peroxide sensor for an exhaled breath analysis system. Electrophoresis\| PubMed ID: 22949159	2012
Improved conversion rates in drug screening applications using miniaturized electrochemical cells with frit channels. Analytical chemistry\| PubMed ID: 23020795	2012
Lactate biosensors: current status and outlook. Analytical and bioanalytical chemistry\| PubMed ID: 24037614	2014
No more conventional reference electrode: transition time for determining chloride ion concentration. Analytica chimica acta\| PubMed ID: 24703217	2014
Mass spectrometric detection of short-lived drug metabolites generated in an electrochemical microfluidic chip. Analytical chemistry\| PubMed ID: 25531627	2015
Sensor-actuator system for dynamic chloride ion determination. Analytica chimica acta\| PubMed ID: 26320957	2015

Wouter Olthuis

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