On the surface modification of microchannels for microcapillary electrophoresis chips

This paper presents systematic investigation of the microchannel surface properties in microCE chips. Three popular materials for microCE chips, polydimethylsiloxane (PDMS), quartz, and glass, are used. The zeta potentials of these microchannels are calculated by measuring the EOF velocity to evaluate the surface properties after surface modification. The hydrophobic PDMS is usually plasma-treated for microCE applications. In this study, a new method using a high-throughput atmospheric plasma generator is adopted to treat the PDMS surface under atmospheric conditions. In this approach, the cost and time for surface treatment can be significantly reduced compared with the conventional vacuum plasma generator method. Experimental results indicate that new functional groups could be formed on the PDMS surface after treatment, resulting in a change in the surface property. The time-dependent surface property of the plasma-treated PDMS is then measured in terms of the zeta potential. Results show that the surface property will reach a stable condition after 1 h of plasma treatment. For glass CE chips, two new methods for changing the microchannel surface properties are developed. Instead of using complicated and time-consuming chemical silanization procedures for CE channel surface modification, two simple and reliable methods utilizing organic-based spin-on-glass and water-soluble acrylic resin are reported. The proposed method provides a fast batch process for controlling the surface properties of glass-based CE channels. The proposed methods are evaluated using PhiX-174 DNA maker separation. The experimental data show that the surface property is modified and separation efficiency greatly improved. In addition, the long-term stability of both coatings is verified in this study. The methods proposed in this study show potential as an excellent solution for glass-based microCE chip surface modification.     

Probabilistic peak detection in CE‐LIF for STR DNA typing

In this work, we present a novel probabilistic peak detection algorithm based on a Bayesian framework for forensic DNA analysis. The proposed method aims at an exhaustive use of raw electropherogram data from a laser‐induced fluorescence multi‐CE system. As the raw data are informative up to a single data point, the conventional threshold‐based approaches discard relevant forensic information early in the data analysis pipeline. Our proposed method assigns a posterior probability reflecting the data point's relevance with respect to peak detection criteria. Peaks of low intensity generated from a truly existing allele can thus constitute evidential value instead of fully discarding them and contemplating a potential allele drop‐out. This way of working utilizes the information available within each individual data point and thus avoids making early (binary) decisions on the data analysis that can lead to error propagation. The proposed method was tested and compared to the application of a set threshold as is current practice in forensic STR DNA profiling. The new method was found to yield a significant improvement in the number of alleles identified, regardless of the peak heights and deviation from Gaussian shape.     

Extending the application potential of capillary electrophoresis/frontal analysis for drug-plasma protein studies by combining it with mass spectrometry detection

CE/frontal analysis (CE/FA) is probably one of the most frequently used modes of CE for studying affinity interactions. It is typically performed with classic UV-Vis detection that suffers from low concentration sensitivity. To overcome this limitation, the applicability of CE/FA in combination with ESI-MS detection for the investigation of drug–HSA interactions was demonstrated. The developed new method combines the advantages of CE/FA, such as low sample consumption and no labeling or immobilization of interacting partners, with the benefits of MS detection, such as higher selectivity and sensitivity; moreover, it can be used for molecules lacking a fluorophore or chromophore. The binding parameters of tolbutamide (TL) and glimepiride (GLP), first- and second-generation antidiabetics that differ strongly in their solubility in aqueous solutions, were investigated by this CE/FA-MS method. This method, in contrast to the CE/FA method with the most commonly used UV-Vis detection, is more sensitive; an almost three times lower LOD was reached. The binding parameters of TL and GLP were investigated by this CE/FA-MS method and compared with the literature data. The binding constant value of TL obtained by UV-Vis detection was lower than the value obtained by the method hyphenated with MS detection, which is probably given by the influence of the ESI parameters on the stability of drug–HSA complex. In addition, the ratio of TL and HSA concentrations was divergent in both of the experimental approaches. Finally, it can be concluded that both detection methods have their strengths and weaknesses.     

An assisted approach of the global optimization for the experimental conditions in capillary electrophoresis

Experimental conditions have effect on the separation of capillary electrophoresis (CE) directly. In this work, a set of index to describe the separation in CE was established properly. Based on a combination of genetic algorithm and least square support vector machine, an assisted approach of global optimization for experimental conditions was proposed for the first time, and it was applied to the separation of four synthetic compounds by CE in nonaqueous system. Under the optimum conditions obtained by this approach, the result of the experiment was satisfactory and proved that this novel approach was effective. Furthermore, we investigated the most important conditions that mainly affect the separation effectiveness of CE by partial least squares regression analysis. Because of the generalization of this new approach proposed, it can be applied to the optimization of other experimental processes.     

Capillary electrophoretic determination of thiosulfate,sulfide and sulfite using in-capillary derivatization with iodine

A new capillary electrophoresis (CE) method was developed for the rapid, simple and selective determination of thiosulfate, sulfide and sulfite species. The proposed method is based on the in-capillary derivatization of separated sulfur anions by mixing their zones with the iodine zone during the electrophoretic migration and direct UV detection of iodide formed. The optimal conditions for the separation and derivatization reaction were established by varying electrolyte pH, electrolyte counter-ion, concentration of iodine, and applied voltage. The optimized separations were carried out in 20 mmol/L Tris-chloride electrolyte (pH 8.5) using direct UV detection at 214 nm. All three sulfur species were well resolved in less than 4 min. The method gives repeatability comparable or even better than this obtained for sulfur anions using standard CE technique. The proposed CE system was applied to the monitoring of sulfur anions in spent fixing solutions during the electrolytic oxidation.     

A Film Model of Sound Propagation in Gas–Liquid Foams: 1. The Sound Velocity

A new (film) model is proposed for the propagation of sound vibrations in gas–liquid foams. The model explains the effect of sound retardation in foams and qualitatively agrees with the experimental data on the velocity of sound propagation in foams of various structures.     

Accelerated multiple-pass moving average: a novel algorithm for baseline estimation in CE and its application to baseline correction on real-time bases

We present a novel algorithm for baseline estimation in CE. The new algorithm which we have named as accelerated multiple-pass moving average (AMPMA) is combined to three preexisting low-pass filters, spike-removal, moving average, and multi-pass moving average filter, to achieve real-time baseline correction with commercial instrumentation. The successful performance of AMPMA is demonstrated with simulated and experimental data. Straightforward comparison of experimental data clearly shows the improvement AMPMA provides to the linear fitting, LOD, and accuracy (absolute error) of CE analysis.     

Application of a modified simplex method to the multivariable optimization of a new FIA system for the determination of osmium

A methodology based on the coupling of experimental design and a modified simplex method is proposed for the optimization of a new flow injection-kinetic system for the spectrophotometric determination of Os (IV) with m-acetylchlorophosphonazo, which has for the first time been used as chromogenic reagent in the quantitative analysis of this element. An orthogonal array design is utilized to design the experimental protocol, in which six variables are varied simultaneously, and obtain the initial simplex using 25 experiments. A modified simplex method is applied to continuously optimize the data of the orthogonal array design; the search for optimum conditions of 6 variables using the modified simplex method required only 25 experiments. The efficiency and simplicity of the coupling of the experimental design and the modified simplex method are attractive for the development of new analytical methods. The method has been applied to the determination of Os (IV) in a refined ore as well as in a secondary alloy and provided satisfactory results.     

毛细管电泳用于药物分析的研究进展

药物分析是毛细管电泳（CE）的重要应用领域,所有CE分离模式与检测方法都在各种药物及其不同形式样品的分离分析中显示出特色和应用能力。该文从药品分析领域中的小分子药物（包括手性药物）及其有关物质、中药与天然产物、体内药物分析、生物制品药物分析等几个方面,综述了近几年CE在这些传统药物分析领域应用的研究进展。限于篇幅,未包括现代药物分析研究比较活跃的理化常数测定、亲和毛细管电泳与结合常数研究（药物与受体间的相互作用等）、临床生物标志物分析、代谢组学和微流控芯片CE分析等方面的内容。根据目前传统药物分析领域的发展,该文关注到近期CE在顺应药物分析的法规需求、电容耦合非接触电导检测（CE-C⁴ D）、改进检测灵敏度与精密度、CE-十二烷基硫酸钠（SDS）毛细管电泳、全柱成像毛细管等电聚焦（icIEF）、抗体分析等方面的新进展。该文结合文献,讨论了目前传统药物分析领域的需求,以及CE在其中的地位、挑战和机遇。对目前CE主要作为互补分析方法在化学药和中药分析中的应用研究提出了一些针对性的建议,期待CE在生物制品分析中的特色和能力得到进一步的发挥,同时提出CE-MS和对CE分析重复性改进等新进展可能对未来CE应用领域的大幅度扩展。该综述主要涉及近3年（2017年1月到2020年2月）及部分2016年的相关文献。     

Application of a modified simplex method to the multivariable optimization of a new FIA system for the determination of osmium

A methodology based on the coupling of experimental design and a modified simplex method is proposed for the optimization of a new flow injection-kinetic system for the spectrophotometric determination of Os (IV) with m-acetylchlorophosphonazo, which has for the first time been used as chromogenic reagent in the quantitative analysis of this element. An orthogonal array design is utilized to design the experimental protocol, in which six variables are varied simultaneously, and obtain the initial simplex using 25 experiments. A modified simplex method is applied to continuously optimize the data of the orthogonal array design; the search for optimum conditions of ¶6 variables using the modified simplex method required only 25 experiments. The efficiency and simplicity of the coupling of the experimental design and the modified simplex method are attractive for the development of new analytical methods. The method has been applied to the determination of Os (IV) in a refined ore as well as in a secondary alloy and provided satisfactory results.     

CE chips fabricated by injection molding and polyethylene/thermoplastic elastomer film packaging methods

This study presents a new packaging method using a polyethylene/thermoplastic elastomer (PE/TPE) film to seal an injection-molded CE chip made of either poly(methyl methacrylate) (PMMA) or polycarbonate (PC) materials. The packaging is performed at atmospheric pressure and at room temperature, which is a fast, easy, and reliable bonding method to form a sealed CE chip for chemical analysis and biomedical applications. The fabrication of PMMA and PC microfluidic channels is accomplished by using an injection-molding process, which could be mass-produced for commercial applications. In addition to microfluidic CE channels, 3-D reservoirs for storing biosamples, and CE buffers are also formed during this injection-molding process. With this approach, a commercial CE chip can be of low cost and disposable. Finally, the functionality of the mass-produced CE chip is demonstrated through its successful separation of phiX174 DNA/HaeIII markers. Experimental data show that the S/N for the CE chips using the PE/TPE film has a value of 5.34, when utilizing DNA markers with a concentration of 2 ng/microL and a CE buffer of 2% hydroxypropyl-methylcellulose (HPMC) in Tris-borate-EDTA (TBE) with 1% YO-PRO-1 fluorescent dye. Thus, the detection limit of the developed chips is improved. Lastly, the developed CE chips are used for the separation and detection of PCR products. A mixture of an amplified antibiotic gene for Streptococcus pneumoniae and phiX174 DNA/HaeIII markers was successfully separated and detected by using the proposed CE chips. Experimental data show that these DNA samples were separated within 2 min. The study proposed a promising method for the development of mass-produced CE chips.     

On-line preparation of microsamples prior to CE

An experimental setup is presented here for the automated analysis of microsamples, based on the on-line coupling of a capillary SPE module and a CE unit using a two-position six-port valve, an open-closed valve to isolate electrically the sample preparation from the CE unit and a "T" interface. A C18 trapping microcolumn (dimensions 2.5 cm x 100 microm id x 360 microm od) was used for the SPE step. The utility of the proposed experimental setup was demonstrated by applying it to the determination of quinolone antibiotics in serum microsamples, which was efficiently carried out in less than 20 min (4 min for protein denaturation and 15 min for analytes preconcentration and CE-UV separation-determination). A complete optimization study was performed for preconcentration and cleanup of quinolones, the coupling of sample preparation module to the CE unit and electrophoretic separation of quinolones. A preconcentration factor of 10.4 was achieved. The volume injected with the proposed method was 125 nL versus 160 nL introduced by hydrodynamic injection. The volume required for the analysis was 2 microL, which makes the proposed experimental setup very useful for the analysis of microsamples in fields of current interest such as metabolomics or proteomics.     

Effect of various modes of pressurization on the separation in capillary electrochromatography

The dissociation constants of 10 sulfonated azo dyes, six of the most common food colours used as additives (Food Yellow 4, Food Yellow 3, Food Red 9, Food Red 7, Food Red 17 and Food Blue 5), and four commonly used as textile dyes (Acid Orange 7, Acid Orange 12, Acid Red 26 and Acid Red 88), have been determined by two different systems, one by using capillary electrophoresis (CE) with diode array detection and the other by using UV-visible absorption spectrophotometry, which has been used as reference method to obtain the pKa values. The pKa values obtained by CE were determined in two ways, first on the basis of the electrophoretic mobilities (calculated from the migration times), and after we propose a new methodology, in which the dissociation constants are determined from the spectra corresponding to the maxima of electrophoretic peaks. The pKa values obtained by using these CE methods have been compared with those obtained by using the spectrophotometric method. The results show that the pKa values obtained by the CE proposed method are in general closer to the reference values than those obtained from the electrophoretic mobilities. Moreover, the proposed method retains the advantages of CE, as the possibility of working with small amounts of sample, despite its purity.     

Evaluation of chromatographic versus electrophoretic behaviour of a series of therapeutical peptide hormones

In this work, models describing the effect of pH on chromatographic and electrophoretic behaviour for a series of polyprotic therapeutic peptide hormones were compared. taking into account the species in solution and the activity coefficients. The usefulness of the proposed equations is twofold, they permit the determination of the acidity constants in water and in the hydroorganic mobile phases used in liquid chromatography (LC) and capillary electrophoresis (CE) and can also be used for the selection of the optimum pH for the separation of mixtures of the modelled compounds. The proposed relationships allow an important reduction of the experimental data needed for the development of new separation methods. The accuracy of the proposed equations is verified by modelling the chromatographic and electrophoretic behaviour of a series of polyprotic therapeutic peptide hormones. By calculating the values of predicted resolutions, selection of the optimum pH to perform LC or CE separations of their mixtures becomes a rapid and simple process.     

Computer simulation of different modes of ACE based on the dynamic complexation model

Several modes of the often used ACE processes are simulated based on the principle of dynamic complexation of interacting species in a capillary column. The model is built on the mass transfer equation, to provide insight into the detailed analyte migration and interaction processes in CE. Normal ACE, Hummel-Dreyer method, vacancy affinity CE, vacancy peak method, and CE frontal analysis are simulated based on typical ACE conditions, and the results are compared with the detector responses of real CE processes using BSA and warfarin as a model system. Remarkable resemblance between the simulated results and the experimental observations was demonstrated for well-buffered ACE systems.     

Quantification of components in overlapping peaks from capillary electrophoresis by using continues wavelet transform method

The application of continues wavelet transform (CWT) for resolving overlapping peaks from capillary electrophoresis (CE) is described. Overlapping peaks can be resolved easily by transforming experimental signals into their wavelet coefficients. The proposed method was applied for the determination of benzoic acid and salicylic acid in overlapping peaks from CE. The composition of the two acids in Zuguangsan, a traditional Chinese patent medicine, was determined. The quantification results are satisfactory. CWT has been shown to be a practicable approach for resolving overlapping peaks and for quantitative determining coeluted compounds in overlapping peaks from CE. The quantification results obtained from CWT were compared with those obtained from numerical differentiation method. CWT has been shown prior to numerical differentiation method for processing experimental signals which contain noise.     

Sequential injection chromatography against HPLC and CE: Application to separation and quantification of amoxicillin and clavulanic acid

Sequential injection chromatography (SIC) has been recently proposed as an alternative separation technique. SIC has the advantages of inexpensiveness, rapid operation procedure, small dimension, short stabilization time, friendly maintenance process and less reagent consumption. In contrast, SIC has had suffered from some limitations. In the current study, a higher pressure resistant selection valve with additional ports than that available in commercially SIC systems was installed. This development allows achieving solution propulsion without showing leakage and linking more standard/sample solutions. In addition, a new method for the separation and quantification of amoxicillin and clavulanic acid in pharmaceutical formulations has been optimized and validated. A comparative study on the efficiency of the SIC method with previous HPLC and CE methods was conducted as well. Besides the benefits of the instrumentation of SIC, the proposed method has shown some advantages over previous HPLC and CE methods with respect to reagent consumption and sample frequency. Other such analytical characters of the SIC method as resolution, peak symmetry, number of theoretical plates, linearity range, accuracy, precision and limits of detection and quantification, recorded comparable results with those obtained from previous HPLC and CE methods.     

All-numerical noise filtering of fluorescence signals for achieving ultra-low limit of detection in biomedical applications

We present an all-numerical method for post-processing of the fluorescent signal as obtained from labeled molecules by capillary electrophoresis (CE) in an optofluidic chip, on the basis of data filtering in the Fourier domain. It is shown that the method outperforms the well-known lock-in amplification during experiments in the reduction of noise by a factor of (square root)2. The method is illustrated using experimental data obtained during CE separation of molecules from a commercial DNA ladder with 17 fluorescently labeled molecules having different base-pair sizes. An improvement in signal-to-noise ratio by a factor of ～10 is achieved, resulting in a record-low limit of detection of 210 fM.     

Synthesis of mesoporous silica and its modification of bismaleimide/cyanate ester resin with improved thermal and dielectric properties

A novel method is proposed to synthesize new mesoporous silica containing amine groups (MPSA), and it was further employed to modify bismaleimide‐dialllyl bisphenol (BD)/cyanate ester (CE) resin to form novel MPSA/BD/CE hybrids; in addition, the typical properties of MPSA/BD/CE were systematically investigated. Results show that these hybrids have very low dielectric constant and loss as well as good thermal properties. Compared with BD/CE resin, all hybrids have not only decreased dielectric constant and loss but also similar dependence of dielectric properties on frequency over the whole frequency from 10 to 10⁶ Hz. Specifically, with the addition of MPSA to BD/CE resin, the dielectric constant reduces from 3.5 to 3.0, and the dielectric loss is only 85% of that of BD/CE resin. Note that all hybrids show better thermal resistance (reflected by higher glass transition temperature, decreased maximum degradation rate, and higher char yield at 800°C) than BD/CE resin. All these differences in macro‐properties are attributed to the different structure between MPSA/BD/CE hybrids and BD/CE resin. Copyright © 2011 John Wiley & Sons, Ltd.     

Carbon nanotubes as SPE sorbents for the extraction of salicylic acid from river water

This paper deals with the ability of different types of carbon nanotubes to adsorb salicylic acid in river water samples. The use of these nanoparticles as a sorbent in a SPE procedure prior to CE analysis is essential for improving the enrichment factor and the recovery values. Several experimental variables were optimized in order to maximize the extraction efficiency. The proposed analytical method is simple, fast, and entails low solvent consumption. Furthermore, salicylic acid could be extracted from river water providing good recovery values in the range from 76.2 to 102.0% (RSD<8.2%). The combination of the specific chemical properties of analyte and the unique physicochemical features of carbon nanotubes sheds new light on the use of these nanoparticles as excellent sorbent materials of pharmaceutical compounds in environmental matrices.