154 research outputs found
Reverse Current Pulse Method To Restore Uniform Concentration Profiles in Ion-Selective Membranes. 1. Galvanostatic Pulse Methods with Decreased Cycle Time
The applications of ion-selective electrodes (ISEs) have been broadened through the introduction of galvanostatic current pulse methods in potentiometric analysis. An important requirement in these applications is the restoration of the uniform equilibrium concentration profiles in the ISE membrane between each measurement. The simplest restoration method is zero-current relaxation, in which the membrane relaxes under open-circuit conditions in a diffusion-controlled process. This paper presents a novel restoration method using a reverse current pulse. An analytic model for this restoration method is derived to predict the concentration profiles inside ISE membranes following galvanostatic current pulses. This model allows the calculation of the voltage transients as themembrane voltage relaxes back toward its zero-current equilibrium value. The predicted concentration profiles and voltage transients are confirmed using spectroelectrochemical microscopy (SpECM). The reverse current restoration method described in this paper reduces the voltage drift and voltage error by 10-100 times compared to the zero-current restoration method. Therefore, this new method provides faster and more reproducible voltage measurements in most chronopotentiometric ISE applications, such as improving the detection limit and determining concentrations and diffusion coefficients of membrane species. One limitation of the reverse current restoration method is that it cannot be used in a few applications that require background electrolyte loaded membranes without excess of lipophilic cation exchanger. © 2009 American Chemical Society
Ann Lab Med
Characterized reference materials (RMs) are needed for clinical laboratory test development and validation, quality control procedures, and proficiency testing to assure their quality. In this article, we review the development and characterization of RMs for clinical molecular genetic tests. We describe various types of RMs and how to access and utilize them, especially focusing on the Genetic Testing Reference Materials Coordination Program (Get-RM) and the Genome in a Bottle (GIAB) Consortium. This review also reinforces the need for collaborative efforts in the clinical genetic testing community to develop additional RMs
Reverse current pulse method to restore uniform concentration profiles in ion-selective membranes. 2. Comparison of the efficiency of the different protocols
The membrane potential of ion-selective electrodes is measured at zero current in traditional potentiometric analysis. Recently, pulsed potentiometric methods have gained importance. In pulsed potentiometric methods, the voltage measured at the end of a current pulse is usually the analytical signal. The applied current alters the concentration profiles inside the sensing membrane. For reproducible voltage measurements the original concentration profiles must be restored in the membrane between current pulses. The simplest restoration method is the zero-current relaxation. Unfortunately, the zero-current method is very slow, which limits the frequency of measurements. In analytical practice the controlled voltage restoration method is most commonly used, but the controlled voltage method has no adequate theoretical description. This paper presents a finite element model of the controlled voltage method to predict its efficiency. The model demonstrates for the first time that increasing membrane resistance decreases the efficiency of this restoration method. The model allows estimating the necessary restoration time for voltage errors below an acceptable threshold value and provides guidance for minimizing the voltage error. The efficiency of the controlled voltage method is compared to the reverse current pulse restoration method discussed in part 1 of this set of papers. It is found that the reverse current restoration method is simpler, requires shorter restoration times (i.e., it allows higher measurement frequency), and it has 4 and 10 times smaller voltage errors compared to the controlled voltage method. These theoretical results are confirmed experimentally. The only limitation of the reverse current pulse restoration method is that it cannot be used with membranes containing a background electrolyte (R+R-) but no excess lipophilic cation exchanger (R-). However, lipophilic cation exchanger can often be added to the membrane to reduce restoration times by allowing the reverse current pulse method to be used. © 2009 American Chemical Society
Genomes in a bottle: creating standard reference materials for genomic variation - why, what and how?
Advancing Benchmarks for Genome Sequencing
Several recent benchmarking efforts provide reference datasets and samples to improve genome sequencing and calling of germline and somatic mutations
Current-polarized ion-selective membranes: The influence of plasticizer and lipophilic background electrolyte on concentration profiles, resistance, and voltage transients
Lipophilic background electrolytes consisting of a lipophilic cation and a lipophilic anion, such as tetradodecylammonium tetrakis(4-chlorophenyl) borate (ETH 500), or bis(triphenylphosphoranylidene) ammonium tetrakis[3, 5bis(trifluoromethyl) phenyl] borate (BTPPATFPB) are incorporated into the membranes of ion-selective electrodes (ISEs) to improve the detection limit and selectivity of the electrodes and decrease the resistance of the sensing membrane. In this work, spectroelectrochemical microscopy (SpECM) is used in conjunction with chronopotentiometry to quantify the effects of a lipophilic background electrolyte on the concentration profiles induced inside current-polarized membranes and on the measured voltage transients in chronopotentiometric experiments. In agreement with the theoretical model, the lipophilic background electrolyte incorporated into o-NPOE or DOS plasticized membranes decreases the membrane resistance and thus the contribution of migration in the overall transport across ion-selective membranes. Consequently, it has a significant influence on the changing concentration profiles of the ion-ionophore complex during chronopotentiometric experiments. © 2009 Elsevier B.V. All rights reserved
Reverse Current Pulse Method To Restore Uniform Concentration Profiles in Ion-Selective Membranes. 2. Comparison of the Efficiency of the Different Protocols
The membrane potential of ion-selective electrodes is measured at zero current in traditional potentiometric analysis. Recently, pulsed potentiometric methods have gained importance. In pulsed potentiometric methods, the voltage measured at the end of a current pulse is usually the analytical signal. The applied current alters the concentration profiles inside the sensing membrane. For reproducible voltage measurements the original concentration profiles must be restored in the membrane between current pulses. The simplest restoration method is the zero-current relaxation. Unfortunately, the zero-current method is very slow, which limits the frequency of measurements. In analytical practice the controlled voltage restoration method is most commonly used, but the controlled voltage method has no adequate theoretical description. This paper presents a finite element model of the controlled voltage method to predict its efficiency. The model demonstrates for the first time that increasing membrane resistance decreases the efficiency of this restoration method. The model allows estimating the necessary restoration time for voltage errors below an acceptable threshold value and provides guidance for minimizing the voltage error. The efficiency of the controlled voltage method is compared to the reverse current pulse restoration method discussed in part 1 of this set of papers. It is found that the reverse current restoration method is simpler, requires shorter restoration times (i.e., it allows higher measurement frequency), and it has 4 and 10 times smaller voltage errors compared to the controlled voltage method. These theoretical results are confirmed experimentally. The only limitation of the reverse current pulse restoration method is that it cannot be used with membranes containing a background electrolyte (R+R−) but no excess lipophilic cation exchanger (R−). However, lipophilic cation exchanger can often be added to the membrane to reduce restoration times by allowing the reverse current pulse method to be used
Reverse Current Pulse Method To Restore Uniform Concentration Profiles in Ion-Selective Membranes. 1. Galvanostatic Pulse Methods with Decreased Cycle Time
The applications of ion-selective electrodes (ISEs) have been broadened through the introduction of galvanostatic current pulse methods in potentiometric analysis. An important requirement in these applications is the restoration of the uniform equilibrium concentration profiles in the ISE membrane between each measurement. The simplest restoration method is zero-current relaxation, in which the membrane relaxes under open-circuit conditions in a diffusion-controlled process. This paper presents a novel restoration method using a reverse current pulse. An analytic model for this restoration method is derived to predict the concentration profiles inside ISE membranes following galvanostatic current pulses. This model allows the calculation of the voltage transients as the membrane voltage relaxes back toward its zero-current equilibrium value. The predicted concentration profiles and voltage transients are confirmed using spectroelectrochemical microscopy (SpECM). The reverse current restoration method described in this paper reduces the voltage drift and voltage error by 10−100 times compared to the zero-current restoration method. Therefore, this new method provides faster and more reproducible voltage measurements in most chronopotentiometric ISE applications, such as improving the detection limit and determining concentrations and diffusion coefficients of membrane species. One limitation of the reverse current restoration method is that it cannot be used in a few applications that require background electrolyte loaded membranes without excess of lipophilic cation exchanger
The creative reconstruction of the Internet: Google and the privatization of cyberspace and digiplace
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CAGI, the Critical Assessment of Genome Interpretation, establishes progress and prospects for computational genetic variant interpretation methods
Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. Results Performance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic. Conclusions Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.Fil: Jain, Shantanu. No especifíca;Fil: Bakolitsa, Constantina. No especifíca;Fil: Brenner, Steven E.. No especifíca;Fil: Radivojac, Predrag. No especifíca;Fil: Moult, John. No especifíca;Fil: Repo, Susanna. No especifíca;Fil: Hoskins, Roger A.. No especifíca;Fil: Andreoletti, Gaia. No especifíca;Fil: Barsky, Daniel. No especifíca;Fil: Chellapan, Ajithavalli. No especifíca;Fil: Chu, Hoyin. No especifíca;Fil: Dabbiru, Navya. No especifíca;Fil: Kollipara, Naveen K.. No especifíca;Fil: Ly, Melissa. No especifíca;Fil: Neumann, Andrew J.. No especifíca;Fil: Pal, Lipika R.. No especifíca;Fil: Odell, Eric. No especifíca;Fil: Pandey, Gaurav. No especifíca;Fil: Peters Petrulewicz, Robin C.. No especifíca;Fil: Srinivasan, Rajgopal. No especifíca;Fil: Yee, Stephen F.. No especifíca;Fil: Yeleswarapu, Sri Jyothsna. No especifíca;Fil: Zuhl, Maya. No especifíca;Fil: Adebali, Ogun. No especifíca;Fil: Fornasari, Maria Silvina. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Patra, Ayoti. No especifíca;Fil: O'Donnell Luria, Anne. No especifíca;Fil: Ng, Pauline C.. No especifíca;Fil: Shon, John. No especifíca;Fil: Veltman, Joris. No especifíca;Fil: Zook, Justin M.. No especifíca
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