Contactless Conductivity Detection in Capillary Electrophoresis: A Review

The popularity of contactless conductivity detection in capillary electrophoresis has been growing steadily over the last few years. Improvements have been made in the design of the detector in order to facilitate its handling, to allow easy incorporation into available instruments or to achieve higher sensitivity. The understanding of its fundamental working principles has been advanced and the detection approach has also been transferred to lab‐on‐chip devices. The range of applications has been extended greatly from the initial work on small inorganic ions to include organic species and biomolecules. Concurrent determination of cations and anions by dual injection from opposite ends has been demonstrated as well as sample introduction by using flow‐injection systems for easy automation of the process.     

毛细管电泳-电容耦合非接触电导检测方法

介绍了电容耦合非接触电导检测(C4D)的检测原理及其最新的研究进展,引用文献50篇。C4D是近几年发展起来的一种用于毛细管电泳和微流控芯片电泳的新检测技术。C4D检测器的原理清楚,结构简单,易于微型化、集成化,不污染检测电极,因而很有应用价值。     

Simultaneous determination of caffeine,paracetamol, and ibuprofen in pharmaceutical formulations by high‐performance liquid chromatography with UV detection and by capillary electrophoresis with conductivity detection

Paracetamol, caffeine and ibuprofen are found in over‐the‐counter pharmaceutical formulations. In this work, we propose two new methods for simultaneous determination of paracetamol, caffeine and ibuprofen in pharmaceutical formulations. One method is based on high‐performance liquid chromatography with diode‐array detection and the other on capillary electrophoresis with capacitively coupled contactless conductivity detection. The separation by high‐performance liquid chromatography with diode‐array detection was achieved on a C₁₈ column (250×4.6 mm², 5 μm) with a gradient mobile phase comprising 20–100% acetonitrile in 40 mmol L^?1 phosphate buffer pH 7.0. The separation by capillary electrophoresis with capacitively coupled contactless conductivity detection was achieved on a fused‐silica capillary (40 cm length, 50 μm i.d.) using 10 mmol L^?1 3,4‐dimethoxycinnamate and 10 mmol L^?1 β‐alanine with pH adjustment to 10.4 with lithium hydroxide as background electrolyte. The determination of all three pharmaceuticals was carried out in 9.6 min by liquid chromatography and in 2.2 min by capillary electrophoresis. Detection limits for caffeine, paracetamol and ibuprofen were 4.4, 0.7, and 3.4 μmol L^?1 by liquid chromatography and 39, 32, and 49 μmol L^?1 by capillary electrophoresis, respectively. Recovery values for spiked samples were between 92–107% for both proposed methods.     

Determination of oxalate and citrate in urine by capillary electrophoresis using solid‐phase extraction and capacitively coupled contactless conductivity based on an improved mini‐cell

A new method for the rapid determination of the metabolites oxalate and citrate in urine samples was based on capillary electrophoresis and capacitively coupled contactless conductivity detection coupled with solid‐phase extraction. The detection cell for capacitively coupled contactless conductivity detection was improved with a smaller inner volume (1.5 nL), reduced noise (0.2∼0.5 mV) and better reproducibility and durability. Under optimal conditions, oxalate and citrate can achieve baseline separation within 4 min and the detection limits (S/N = 3) for oxalate and citrate are about 44 and 244 ng/mL, respectively. The overall recovery is between 80.0 and 89.2%. This method offers a better choice for quantitative analysis of strong anions such as oxalate and citrate in diagnostic testing associated with human diseases.     

Simple in‐house flow‐injection capillary electrophoresis with capacitively coupled contactless conductivity method for the determination of colistin

An in‐house flow‐injection capillary electrophoresis with capacitively coupled contactless conductivity detection method was developed for the direct measurement of colistin in pharmaceutical samples. The flow injection and capillary electrophoresis systems are connected by an acrylic interface. Capillary electrophoresis separation is achieved within 2 min using a background electrolyte solution of 5 mM 2‐morpholinoethanesulfonic acid and 5 mM histidine (pH 6). The flow‐injection section allows for convenient filling of the capillary and sample introduction without the use of a pressure/vacuum manifold. Capacitively coupled contactless conductivity detection is employed since colistin has no chromophore but is cationic at pH 6. Calibration curve is linear from 20 to 150 mg/L, with a correlation coefficient (r²) of 0.997. The limit of quantitation is 20 mg/L. The developed method provides precision, simplicity, and short analysis time.     

Elimination of the artefact peaks in capillary electrophoresis determination of glutamate by using organic solvents in sample preparation

Focusing on the demand from the food industry for fast and reliable alternative methods to control the quality of food products, we present in this paper a method for amino acid separation and glutamic acid quantification in complex matrices employing capillary electrophoresis with capacitively coupled contactless conductivity detection. We demonstrate by simulation and experimentally the use of organic solvents in sample preparation to prevent peak splitting and increase stacking in capillary electrophoretic separations of amino acids. Additionally, we obtained results for glutamic acid quantification comparable to those obtained via traditional methods used at industrial sites. We tested premium and low‐cost samples with large variations in their glutamic acid content, which demonstrated the wide range of applicability of the method presented herein. The results of the proposed capacitively coupled contactless conductivity detection based capillary electrophoresis method agreed with those obtained by an enzymatic detector and ultra high performance liquid chromatography coupled to tandem mass spectrometry, considering a confidence level of 95%.     

电泳芯片无接触电导检测器的理论研究

目前电泳芯片大多数采用的是光学检测的方法,这为电泳芯片的微型化、一体化集成带来了一定的难度。为此,设计了一种新的电泳芯片高频无接触电导检测器,并对这种新型的检测器进行了理论研究和分析,建立了高频电导检测器等效电路模型,对高频电导检测器的结构进行了设计;综合考虑区带展宽等因素,确定了检测器的结构尺寸。该检测器具有应用范围广、结构简单、易于一体化集成的特点。     

Application of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE‐C4D): An update

Capacitively coupled contactless conductivity detection (C⁴D) has appeared as a powerful technique for the detection of compounds lacking chromogenic or fluorogenic group. Since our last review (Biomedical Chromatography 2014; 28 : 1502–1506) several new capillary electrophoresis (CE)‐C⁴D methods have been reported. This review provides an update of the most recent utilization of CE‐C⁴D in the field of pharmaceutical, biomedical and food analysis covering the period from February 2014 to October 2016. The use of CE with C⁴D in the pharmaceutical field has been shown in many papers. Examples illustrate the applicability of CE‐C⁴D in the fields of pharmaceutical, biomedical and food analysis. Finally, general conclusions and perspectives are provided.     

A review of the recent achievements in capacitively coupled contactless conductivity detection

Capacitively coupled contactless conductivity detection (C⁴D) in the axial electrode configuration was introduced in 1998 as a quantification method for capillary electrophoresis. Its universality allows the detection of small inorganic ions as well as organic and biochemical species. Due to its robustness, minimal maintenance demands and low cost the popularity of this detector has been steadily growing. Applications have recently also been extended to other analytical methods such as ion chromatography, high-performance liquid chromatography and flow-injection analysis. C⁴D has also found use for detection on electrophoresis based lab-on-chip devices. Theoretical aspects of C⁴D in both the capillary and microchip electrophoresis format have been comprehensively investigated. Commercial devices are now available and the method can be considered a mature detection technique. In this article, the achievements in C⁴D for the time period between September 2004 and August 2007 are reviewed.     

毛细管电泳非接触电导检测法研究电渗流峰变化规律

采用自行研制的非接触电导检测器,结合毛细管电泳技术,以10 mmol/L的2-N-吗啡啉乙磺酸(MES)/L-组氨酸(L-His)为缓冲溶液,系统研究了缓冲溶液浓度、pH值、样品浓度对电渗流峰的变化规律。结果表明:随着样品KCl溶液的浓度的减小,电渗流峰出现由正峰逐渐变为负峰的现象,并结合非接触电导检测原理、L-His的特性和质子平衡方程进行了的解释。     

Advances in amperometric and conductometric detection in capillary and chip-based electrophoresis

Amperometric and conductometric detection are currently the two major electrochemical detection modes in capillary and chip electrophoresis. The ease of miniaturization and integration of electrochemical detection elements offers a high potential for the development of portable analytical devices based on electromigrative separations. The challenges and basic concepts of both detection principles in the context of capillary/chip electrophoresis are shortly introduced and milestones of the methodical developments are summarized from a historical perspective. Recent advances and applications are discussed with more detail. Particular attention is paid to new trends in this area of research such as measurements in short capillaries and the enormous progress and increased popularity of contactless conductivity detection. Correspondence: Frank-Michael Matysik, Institute of Analytical Chemistry, University of Leipzig, Linnéstr. 3, D-04103 Leipzig, Germany     

毛细管电泳无接触电导检测研究进展

毛细管电泳(CE)电导检测(CD)是相对较灵敏和仪器结构简单的一项溶液分析技术,尤其是对于无生色团的无机离子分析更具有突出优势,因此,CE-CD技术近年来得到了较快发展[1],并已推出商品化的毛细管电泳电导检测器[2]。但CE和CD的偶联目前还存在如下几个问题:第一,加工适合于毛细管     

Ultrafast capillary electrophoresis method for the simultaneous determination of ammonium and diphenhydramine in pharmaceutical samples

Ammonium and diphenhydramine are active ingredients commonly found in the same pharmaceutical preparations. We report, for the first time, a sub‐minute method for the simultaneous determination of ammonium and diphenhydramine. The method is based on capillary electrophoresis with capacitively coupled contactless conductivity detection. Both analytes can be quantified in a single run (∼80 injections/h) using 30 mmol/L 2‐(N‐morpholino)ethanesulfonic acid and 15 mmol/L lithium hydroxide (pH 6.0) as background electrolyte. The separation by capillary electrophoresis was achieved on a fused‐silica capillary (50 cm total length, 10 cm effective length, and 50 μm inside diameter). The limits of detection were 0.04 and 0.02 mmol/L for ammonium and diphenhydramine, respectively. The proposed method also provided adequate recovery values for spiked samples (100–106 and 97–104% for ammonium and diphenhydramine, respectively). The results obtained with the new capillary electrophoresis method were compared with those of the high‐performance liquid chromatography method for diphenhydramine and the Kjeldahl method for ammonium and no statistically significant differences were found (95% confidence level).     

毛细管电泳及芯片毛细管电泳的电容耦合非接触电导检测

综述了毛细管电泳(CE)及芯片毛细管电泳(MCE)的电容耦合非接触电导检测(Capacitively Coupled Contactless Conductivity detection,C4D)的研究状况;并分别对其装置、检测的影响因素及其应用进行了评述。引用文献81篇。     

多通道非接触电导检测装置用于自由流电泳分离在线检测

现有自由流电泳(FFE)装置因不具备在线检测功能,其实用性仍然存在明显不足.针对这一问题,该工作发展了一种多通道电容耦合式非接触电导检测(MC-C4 D)装置并开发了自动测量软件.MC-C4 D装置采用了并行分时的非接触电导检测技术,即由多个同样的非接触电导检测模块并行排列,而单个电导检测模块又由多个非接触电导检测池组...     

Referenced Capacitively Coupled Conductivity Detector for Capillary Electrophoresis

A dual capacitively coupled contactless conductivity detector for capillary electrophoresis was developed. The two channels are arranged in a bridge configuration so that one of them acts as a reference whose signal is subtracted. This effectively compensates for the baseline conductivity of the separation buffer so that the electronic zero setting is not necessary. Changes in the buffer composition are automatically accounted for, as are temperature drifts. The system is demonstrated for the detection of inorganic model cations in capillary electrophoresis. Besides the use with two separate capillaries, one of which solely serves as reference, it was also found possible to use a single capillary which is looped back through the reference cell.     

微芯片毛细管电泳快速测定加替沙星注射液中加替沙星的含量

研究了用微芯片毛细管电泳非接触电导检测系统快速测定加替沙星注射液中加替沙星的方法。对缓冲液的类型、浓度、分离电压以及进样时间等因素进行了优化。最佳条件为:缓冲液5.0 mmol/L HAc,分离电压2.0 kV,进样时间15.0 s。在该条件下,可在1.0 min内实现加替沙星的快速含量测定。线性范围为4.0～150μg/mL,检出限为1.0μg/mL,加标回收率为95.7%～101%,可成功测定注射液中加替沙星的含量。     

Frequency‐tuned contactless conductivity detector for the electrophoretic separation of clinical samples in capillaries with very small internal dimensions

An axial design of a capacitively coupled contactless conductivity detector was tested in combination with fused‐silica capillaries with internal diameters of 10, 15, and 25 μm, which are used for high‐efficiency electrophoretic separation. The transmission of the signal in the detection probe dependent on the specific conductivity of the solution in the capillary in the range 0–278 mS.m⁻¹ has a complex character and a minimum appears on the curve at very low conductivities. The position of the minimum of the calibration dependence gradually shifts with decreasing frequency of the exciting signal from 1.0 to 0.25 MHz toward lower specific conductivity values. The presence of a minimum on the calibration curves is a natural property of the axial design of contactless conductivity detector, demonstrated by solution of the equivalent electrical circuit of the detection probe, and is specifically caused by the use of shielding foil. The behavior of contactless conductivity detector in the vicinity of the minimum was documented for practical separations of amino acids in solutions of 3.2 M acetic acid with addition of 0–50% v/v methanol.     

Conductivity detection for conventional and miniaturised capillary electrophoresis systems

Since the introduction of capillary electrophoresis (CE), conductivity detection has been an attractive means of detection. No additional chemical properties are required for detection, and no loss in sensitivity is expected when miniaturising the detector to scale with narrow-bore capillaries or even to the microchip format. Integration of conductivity and CE, however, involves a challenging combination of engineering issues. In conductivity detection the resistance of the solution is most frequently measured in an alternating current (AC) circuit. The influence of capacitors both in series and in parallel with the solution resistance should be minimised during conductivity measurements. For contact conductivity measurements, the positioning and alignment of the detection electrodes is crucial. A contact conductivity detector for CE has been commercially available, but was withdrawn from the market. Microfabrication technology enables integration and precise alignment of electrodes, resulting in the popularity of conductivity detection in microfluidic devices. In contactless conductivity detection, the alignment of the electrodes with respect to the capillary is less crucial. Contactless conductivity detection (CCD) was introduced in capillary CE, and similar electronics have been applied for CCD using planar electrodes in microfluidic devices. A contactless conductivity detector for capillaries has been commercialised recently. In this review, different approaches towards conductivity detection in capillaries and chip-based CE are discussed. In contrast to previous reviews, the focus of the present review is on the technological developments and challenges in conductivity detection in CE.     

Optimization of a capillary zone electrophoresis–contactless conductivity detection method for the determination of nisin

Determination of natural preservatives using electrophoretic or chromatographic techniques in fermented milk products is a complex task due to the following reasons: (i) the concentrations of the analytes can be below the detection limits, (ii) complex matrix and comigrating/coeluting compounds in the sample can interfere with the analytes of the interest, (iii) low recovery of the analytes, and (iv) the necessity of complex sample preparation. The aim of this study was to apply capillary zone electrophoresis coupled with contactless conductivity detection for the separation and determination of nisin in fermented milk products. In this work, separation and determination of natural preservative–nisin in fermented milk products is described. Optimized conditions using capillary zone electrophoresis coupled with capacitance‐to‐digital technology based contactless conductivity detector and data conditioning, which filter the noise of the electropherogram adaptively to the peak migration time, allowed precise, accurate, sensitive (limit of quantification: 0.02 μg/mL), and most importantly requiring very minute sample preparation, determination of nisin. Sample preparation includes following steps: (i) extraction/dilution and (ii) centrifugation. This method was applied for the determination of nisin in real samples, i.e. fermented milk products. The values of different nisin forms were ranging from 0.056 ± 0.003 μg/mL to 9.307 ± 0.437 μg/g.