Development and validation of a separation method for the diastereomers and enantiomers of aziridine-type protease inhibitors

Aziridine derivatives are attracting pharmacological interest as protease inhibitors. Due to their two centers of chirality, the aziridines studied here are mixtures of two diastereomers and corresponding enantiomers. Applying cyclodextrin-modified capillary electrophoresis resulted in a baseline separation of the four isomers. The most robust separation was obtained by means of 2 mM sulfated beta-cyclodextrin in 50 mM phosphate buffer of pH 2.5. Using this method, 0.25% of the trans-diastereomers aziridine could be precisely and accurately quantified in the presence of 99.75% of the cis-isomers. The corrected peak-area ratios, migration times, and resolutions were found to be robust with respect to small variations of voltage, buffer concentrations, pH, temperature, chiral selector concentration, and different lots.     

Paper-based Wearable Electrochemical Sensors: A New Generation of Analytical Devices

Over the past few years, the emergence of electrochemical wearable sensors has attracted considerable attention because of their promising application in point-of-care testing due to some features such as high sensitivity, simplicity, miniaturization, and low fabrication cost. Recent developments in new fabrication approaches and innovative substrates have resulted in sensors able to real-time and on-body measurements. Wearable electrochemical sensors have also been combined with paper-based substrates and directly used on human skin for different applications for non-invasive analyses. Furthermore, wearable electrochemical sensors enable monitoring analytes in different biofluids without complex procedures, such as pre-treatment or sample manipulation. The coupling of IoT to various wearable sensors has also attracted attention due to real-time data collection and handling in remote and resource-limited conditions. This mini-review presents the significant advances in developing wearable electrochemical devices, such as sampling, data collection, connection protocols, and power sources, and discusses some critical challenges for higher performance in this field. We also present an overview of the application of paper as an intelligent substrate for electrochemical wearable sensors and discuss their advantages and drawbacks. Lastly, conclude by highlighting the future advances in wearable sensors and diagnostics by coupling real-time and on-body measurements to multiplexed detection of different biomarkers simultaneously, reducing the cost and time of classical analysis to provide fast and complete overall physiological conditions to the wearer.     

测量方法确认技术及其指标评价

阐述了测量方法确认的方法、指标以及方法确认的6种技术手段；介绍了方法确认技术的9种指标以及指标的获得和评价；指出方法确认技术的重点应放在识别和消除显著影响方面。     

Analytical Methodologies with Very Low Blank Levels: Implications for Practical and Empirical Evaluations of the Limit of Detection

Abstract

Limit of detection criteria in analytical chemistry are regularly specified in terms of the distribution of the measured blank response. The consequences of an analytical blank response with a negligible distribution of measured values on the calculation and significance of limit of detection criteria receive scarce attention. A consideration of a hypothetical analytical methodology where the blank response is zero and the distribution of blank values is negligible is described. The impact of this situation on the traditional limit of detection criteria and on calibration relationships is discussed in detail. A simple, empirical method of estimating indicative method detection limits based on whole‐method repeatability is proffered. This model has been validated with experimental data.     

Nitric Oxide Release for Enhanced Biocompatibility and Analytical Performance of Implantable Electrochemical Sensors

The real-time, continuous monitoring of glucose/lactate, blood gases and electrolytes by implantable electrochemical sensors holds significant value for critically ill and diabetic patients. However, the wide-spread use of such devices has been seriously hampered by implant-initiated host responses (e. g., thrombus formation, inflammatory responses and bacterial infection) when sensors are implanted in blood or tissue. As a result, the accuracy and usable lifetime of in vivo sensors are often compromised. Nitric oxide (NO) is an endogenous gas molecule able to inhibit platelet adhesion/activation, inflammatory responses and bacterial growth. As such, the release of NO from the surfaces of in vivo sensors is a promising strategy for enhancement of their biocompatibility and analytical performance. In this review, the physiological functions of NO to improve the biocompatibility of implantable electrochemical sensors are introduced, followed by a brief analysis of chemical approaches to realize NO release from such devices. A detailed summary of the various types of NO releasing electrochemical sensors reported to date and their performance in benchtop and/or in vivo testing are also provided. Finally, the prospects of future developments to further advance NO releasing sensor technology for clinical use are discussed.     

Recent Advances in Electrochemical Sensors for Detecting Weapons of Mass Destruction. A Review

The detection of chemical warfare agents (CWA) has become a worldwide security concern in light of the many recent international threats utilizing nerve agents. Among a variety of detection methods that have been developed for CWA, electrochemical sensors offer the unrivaled merits of high sensitivity, specificity and operational simplicity. Recent insights into novel fabrication methodologies and electrochemical techniques have resulted in the demonstration of electrochemical sensors able to address many of the limitations of conventional methodologies. This article reviews recent advances and developments in the field of electrochemical biosensors based detection of nerve agent and their utility for decentralized threat detection. With continued innovations and attention to key challenges, it is expected that electrochemical sensors will play a pivotal role in the CWA detection scenario. This review concludes with the implications of the electrochemical sensing platforms along with future prospects and challenges.     

Redox Mechanism and Evaluation of Kinetic and Thermodynamic Parameters of 1,3‐Dioxolo[4,5‐g]pyrido[2,3‐b]quinoxaline Using Electrochemical Techniques

The electrochemical behavior of a biologically important heterocyclic compound, 1,3‐dioxolo[4,5‐g]pyrido[2,3‐b]quinoxaline was investigated by cyclic, square wave and differential pulse voltammetry in solutions of different pH. Kinetic and thermodynamic parameters like standard rate constant, diffusion coefficient, apparent energy of activation_, standard Gibbs free energy and enthalpy and entropy changes were evaluated. Limits of detection and quantification were determined by square wave voltammetry. The redox mechanism of the compound was proposed on the basis of experimental results. Computational chemistry was used as a tool for the verification of experimental outcomes and assessment of different theoretical parameters     

Limits of detection and decision. Part 3

It has been shown that the MARLAP (Multi-Agency Radiological Laboratory Analytical Protocols) for estimating the Currie detection limit, which is based on ‘critical values of the non-centrality parameter of the non-central t distribution’, is intrinsically biased, even if no calibration curve or regression is used. This completed the refutation of the method, begun in Part 2. With the field cleared of obstructions, the true theory underlying Currie's limits of decision, detection and quantification, as they apply in a simple linear chemical measurement system (CMS) having heteroscedastic, Gaussian measurement noise and using weighted least squares (WLS) processing, was then derived. Extensive Monte Carlo simulations were performed, on 900 million independent calibration curves, for linear, “hockey stick” and quadratic noise precision models (NPMs). With errorless NPM parameters, all the simulation results were found to be in excellent agreement with the derived theoretical expressions. Even with as much as 30% noise on all of the relevant NPM parameters, the worst absolute errors in rates of false positives and false negatives, was only 0.3%.     

Electrochemical Sensors,a Bright Future in the Fabrication of Portable Kits in Analytical Systems

Analysis of food, pharmaceutical, and environmental compounds is an inevitable issue to evaluate quality of the compounds used in human life. Quality of drinking water, food products, and pharmaceutical compounds is directly associated with human health. Presence of forbidden additives in food products, toxic compounds in water samples and drugs with low quality lead to important problems for human health. Therefore, attention to analytical strategy for investigation of quality of food, pharmaceutical, and environmental compounds and monitoring presence of forbidden compounds in materials used by humans has increased in recent years. Analytical methods help to identify and quantify both permissible and unauthorized compounds present in the materials used in human daily life. Among analytical methods, electrochemical methods have been shown to have more advantages compared to other analytical methods due to their portability and low cost. Most of big companies have applied this type of analytical methods because of their fast and selective analysis. Due to simple operation and high diversity of electroanalytical sensors, these types of sensors are expected to be the future generation of analytical systems. Therefore, many scientists and researchers have focused on designing and fabrication of electroanalytical sensors with good selectivity and high sensitivity for different types of compounds such as drugs, food, and environmental pollutants. In this paper, we described the mechanism and different examples of DNA, enzymatic and electro‐catalytic methods for electroanalytical determination of drug, food and environmental compounds.     

Measurement uncertainty evaluation for a non-negative measurand: an alternative to limit of detection

The interpretation and reporting the results of measurements on materials where the concentration of the analyte is close to or may even be zero has been the subject of much discussion with the use of such concepts as limit of detection (LOD) and limit of quantification (LOQ). While these concepts have taken into account the measurement uncertainty, they have not utilised the fact that the value of the measurand, i.e., the concentration, is constrained to be zero or greater. Taking this into account the distribution of values attributable to the measurand can be derived from the probability density function (PDF) that determines the distribution of the observed values. When this PDF is normal the distribution of the values attributable to the measurand is a truncated t distribution with a lower limit of re-normalised so that the total probability is one, where x _m is the mean of the n observed values and s their standard deviation. When x _m much greater than then the distribution reverts to the unmodified t distribution. The probability that the value of the measurand is above or below a limit can be calculated directly from this truncated t distribution and the interpretation of the result does not require the use of concepts such as LOD and LOQ. Also it deals with the problem of negative observations. This Report was written by Alex Williams (e-mail: aw@camberley.demon.co.uk) for the Statistical Subcommittee and approved by the Analytical Methods Committee.     

Limits of detection and decision. Part 1

Extensive Monte Carlo studies of instrumental limits of detection were performed on a simple univariate chemical measurement system having homoscedastic, Gaussian measurement noise and using ordinary least squares (OLS) processing of tens of millions of independent calibration curve data sets. It was found that prediction interval-based experimental detection limits were significantly negatively biased, in both the net response domain and the chemical content domain, resulting in substantially higher rates of false negatives than specified via customary critical t values. The diagnostic fix for the bias problem provided clear proof that hypothesis-based detection limits need not be unique, even as distributions of random variates, if the alternate hypothesis is non-unique. It was also demonstrated that hypothesis-based decision and detection limits have finite support that does not include the region near zero analyte content, so that both have finite moments and finite confidence intervals.     

Clarification of the limit of detection in chromatography

Summary Current problems with the limit of detection (LOD) concept in chromatography are reviewed. They include the confusion of the LOD with other separate, distinct concepts in trace analysis such as the minimum detectability (MD); the use of arbitrary, unjustified models for the calculation of the LOD; the use of concentration units instead of units of amount; and the failure to account for differences in chromatographic conditions when comparing LODS.Solutions to these LOD problems are discussed. Two models are proposed for calculating the chromatographic LOD. A new concept, the standardized chromatographic LOD, is introduced to account for differences in chromatographic bandwidths of experimentally measured LODs. The standardized chromatographic LOD is shown to be a more reliable parameter than the conventional (non-standardized) chromatographic LOD.This paper is published as a discussion mateiral. We welcome comments from our readers.     

当前疫情下分析化学教学的一点思考

2019年底爆发的新型冠状病毒肺炎席卷了整个中国,在分析化学教学中如何能结合这一热点问题启发学生多方位思考、多角度理解分析化学的一些关键知识点(如3S+2A)并能激发后续学习兴趣,结合在当前肺炎疫情下线上教学的广泛使用,作者对这些相关内容做了一些思考,并在教学过程中进行了尝试。     

Urea Detection of Electrochemical Transistor Sensors based on Polyanline (PANI)/MWCNT/Cotton Yarns

A cotton yarn biosensor based on electrochemical transistor functionalized with MWCNT and PANI was developed for the detection of urea. The transistors based on PANI/MWCNT/cotton yarns under optimized MWCNT concentration has been obtained, which exhibited high on/off current ratio, fast response time, and good operational stability. A transistor-based urea sensor was prepared from PANI/MWCNT/cotton yarns, which could monitor urea in the 1 nM–1 mM linear range with the correlation coefficient of 0.9716. Furthermore, the sensor showed superior reproducibility and high specificity. The practical applications of the proposed sensor were also confirmed. These results indicate the flexible transistor can be used as an efficient platform for biological detection in body fluids.     

A study of the relation between the limit of detection and the limit of quantitation in inductively coupled plasma spectrochemistry

The limit of quantitation based on a repeatability threshold concept is compared with the limit of detection in induction coupled plasma atomic emission spectrometry (ICP-AES) and induction coupled plasma mass spectrometry (ICP-MS). A 5%-based limit of quantitation would normally correspond to 10 times the 3-σ based limit of detection. However, because of a possible lack of linearity of the calibration graph at low concentrations, some additional noise not taken into consideration and the possible use of time-correlated multichannel detection, this ratio of 10 cannot be used in every case. It is suggested that a suitable way of determining the limit of quantitation is to establish the plot of the percentage relative standard deviation (RSD) of the net signal as a function of the concentration in a range from the limit of detection to 50 times this limit.     

毒鼠强薄层色谱分析的检出限

建立薄层色谱法快速对毒鼠强进行简易分析的方法,利用薄层色谱进行层析分离,采用特殊显色方法,对毒鼠强进行显色,以能正常观察到斑点的色泽状态,辅助GC-MS方法确定检出极限。薄层色谱法分析毒鼠强检出限可达5~10μg。能用此方法对大多数中毒案件提取的检材进行定性分析。     

纳米材料电化学与生物传感器——有机微污染物检测新途径

本文介绍了近年来纳米材料电化学与生物传感器在有机微污染物检测中的研究现状,分析了这些传感器中纳米材料修饰电极的特点,重点阐述了纳米材料在有机微污染物检测中的重要作用,列举了一些纳米材料电化学与生物传感器在有机微污染物检测中的应用。最后对纳米材料电化学与生物传感器用于有机微污染物的检测研究进行了简要评述和展望。     

Development of a non-competitive immunoassay for monitoring DDT, its metabolites and analogues in water samples

This report highlights the characteristics of a general method of performing non-competitive immunoassays for low-molecular-mass analytes, which was developed and applied to 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) determination in aqueous samples. The method is based on the separation of the analyte-bound antibody from the excess of the free antibody by a chromatographic step, followed by the dissociation of the complex and the capture of the previously bound antibody on a solid phase. The measured signal is linearly correlated to the concentration of the complex and, consequently, to the analyte concentration. The 3σ limit of detection (LOD, 8 ng l⁻¹) obtained by the above method enabled us to decidedly improve the sensitivity of the corresponding enzyme-linked immunosorbant assay (ELISA) and of all reported immunoassays for DDT.In addition, by applying this new format, even if a very selective antibody was used, a broad selectivity was observed, which allowed DDT + DDD + DDE to be determined instead of only p,p′-DDT as in the ELISA performed with the same antibody. In addition, real water samples were validated in a percentage recovery test. Very good recovery rates were obtained, highlighting the validity of the proposed method to accurately determine the total DDT content in water.