Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation,methodology and applications

Capillary electrophoresis (CE) offers fast and high‐resolution separation of charged analytes from small injection volumes. Coupled to mass spectrometry (MS), it represents a powerful analytical technique providing (exact) mass information and enables molecular characterization based on fragmentation. Although hyphenation of CE and MS is not straightforward, much emphasis has been placed on enabling efficient ionization and user‐friendly coupling. Though several interfaces are now commercially available, research on more efficient and robust interfacing with nano‐electrospray ionization (ESI), matrix‐assisted laser desorption/ionization (MALDI) and inductively coupled plasma mass spectrometry (ICP) continues with considerable results. At the same time, CE‐MS has been used in many fields, predominantly for the analysis of proteins, peptides and metabolites. This review belongs to a series of regularly published articles, summarizing 248 articles covering the time between June 2016 and May 2018. Latest developments on hyphenation of CE with MS as well as instrumental developments such as two‐dimensional separation systems with MS detection are mentioned. Furthermore, applications of various CE‐modes including capillary zone electrophoresis (CZE), nonaqueous capillary electrophoresis (NACE), capillary gel electrophoresis (CGE) and capillary isoelectric focusing (CIEF) coupled to MS in biological, pharmaceutical and environmental research are summarized.     

Sensitivity enhancement in capillary electrophoresis and their applications for analyses of pharmaceutical and related biochemical substances

This review aims to illustrate sensitivity enhancement methods in capillary electrophoresis (CE) and their applications for pharmaceutical and related biochemical substance analyses. The first two parts of the article describe the introduction and principle of CE. The main part focuses on strategies for sensitivity improvement in CE including detector and capillary technologies and preconcentration techniques. Applications of these techniques for pharmaceutical and biomedical substance analyses are surveyed during the years 2018–2021.     

Cover Picture: Electrophoresis 2'09

Regular issues provide a wide range of research and review articles covering all aspects of electrophoresis. Here you will find cutting‐edge articles on methods and theory, instrumentation, nucleic acids, CE and CEC, miniaturization and microfluidics, proteomics and two‐dimensional electrophoresis. Issue no. 2 has a “Fast Track” paper on the attomole protein analysis by capillary isoelectric focusing (CIEF) with LIF detection based on a post‐column sheath flow cuvette employing Chromeo P503 as a fluorogenic reagent for protein labeling before CIEF analysis. Further selected topics of issue 2 are: Influence of image‐analysis software on quantitation of two‐dimensional gel electrophoresis data A PDMS sheath flow cuvette for high‐sensitivity LIF measurements in CE     

Cover Picture: Electrophoresis 12'2010

Issue no. 12 is a regular issue comprising 19 contributions distributed over five distinct parts. Part I has 7 articles describing novel methodologies pertaining to proteins and proteomics. Part II has 3 research papers on CEC stationary phases and CEC‐MS. Part III is on detection approaches including a review article on the advances and applications of chemiluminescence coupled to CE. Part IV has two papers on enantioseparations, and Part V has four contributions on aptamers, human genetic, preparative FFE and microchannels. Featured articles include: Simplified method for concentration of mitochondrial membrane protein complexes (( 10.1002/elps.201000019 )) Analysis of low‐molecular mass aldehydes in drinking waters through capillary electrophoresis with laser‐induced fluorescence detection (( 10.1002/elps.200900734 )) Selection of aptamers for signal transduction proteins by capillary electrophoresis (( 10.1002/elps.200900543 ))     

Recent developments of monolithic and open‐tubular capillary electrochromatography (2017–2019)

Capillary electrochromatography, which combined the high selectivity of high‐performance liquid chromatography and the high separation efficiency of capillary electrophoresis, is an attractive separation tool. In this review, the developments on monolithic and open tubular capillary electrochromatography during 2017 to August 2019 are summarized. Considering the development of novel stationary phases is the most active research field in capillary electrochromatography, monolithic capillary electrochromatography is classified according to the polymer‐based and hybrid monolithic columns, while open‐tubular capillary electrochromatography is categorized by cyclodextrin, silica, polymer, nanomaterials, microporous materials, and biomaterials‐based open tubular columns.     

Open access capillary electrophoresis. A walk up capillary electrophoresis service for the synthetic chemist

A capillary electrophoresis (CE) system has been developed to provide routine purity information to support synthetic organic chemists. A single micellar electrokinetic chromatography system that produces good selectivity with short run times was developed. The instrument operating software has been modified to run separations in a custom open access mode. No expert knowledge of CE is required to run separations.     

Electrophoretically mediated microanalysis

This review describes the existing developments in the use of the capillary electrophoretic microanalytical technique for the in-line study of enzyme reaction, electrophoretically mediated microanalysis (EMMA). The article is divided into a number of parts. After an introduction, the different modes, basic principle, procedure, and some mathematical treatments of EMMA methodology are discussed and illustrated. The applications of EMMA for enzyme assay and for non-enzymatic determination are summarized into two tables. In addition to classical capillary electrophoresis (CE) instrument EMMA, special emphasis is given to a relatively new technique: EMMA on CE microchip. Finally, conclusions are drawn.     

Software and internet resources for capillary electrophoresis and micellar electrokinetic capillary chromatography

The purpose of the contribution is to show how software and the internet have changed the way in which we carry out research, and what additional possibilities these new resources and tools provide. The internet and e-mail broaden our horizon for cooperation. There are no borders for information exchange: our library is a virtual one, electronic databases are at our fingertips. E-mail discussion groups provide an electronic community of CE users. Such forums have provided a basis for worldwide scientific cooperation amongst scientists; the present contribution is only one of several examples. Estimation software provides us with estimates of component properties in those cases where this information is not available from literature or from experiments (an estimated value is better than no value). Several examples will illustrate the use of estimation software in capillary zone electrophoresis and micellar electrokinetic capillary chromatography. Simulation software presents visualization of experimental results to be expected, both as a training tool and as the first step in method development. Other simulations yield valuable insights into phenomena that are not readily accessible experimentally for reasons of size or time-scale.     

Cover Picture: Electrophoresis 14'2011

Issue no. 14 is a regular issue consisting of 17 contributions distributed over 3 distinct parts. Part I has 7 articles describing studies on proteins and proteomics including measuring protein mobility using laser Doppler electrophoresis, high sensitivity protein analysis by FESI‐CE‐MALDI‐MS, protocol for SDS‐PAGE separation of myosin heavy chain isoforms, proteomics analysis of a spring wheat cultivar in response to prolonged cold stress, analysis of changes in the 20S proteasome, treatment of acute lymphoblastic leukemia with L‐asparaginase, and improved method for immunostaining of mucin. Part II is on nucleic acids and has 4 contributions on multiplex PCR‐CE analysis, copy number variation, ethnic difference, SNPs, CE‐SSCP, allelic ladder and SNaPshot technique. Part III has 6 articles on various fundamentals and methodologies, including nanofluidics, nanopore sensing, sequential injection setup for CIEF combined with MS detection, determination of imatinib mesylate in chronic myeloid leukemia patients by CE, UV detection of plasma malondialdehyde using CE‐FASI, enantioseparation of basic drugs by CE using clarithromycin lactobionate chiral selector and CE determination of bioactive constituents in Herba Houttuyniae. Featured articles include: Advances in the measurement of protein mobility using laser Doppler electrophoresis – the diffusion barrier technique (( 10.1002/elps.201100108 )) Improved method for immunostaining of mucin separated by supported molecular matrix electrophoresis by optimizing the matrix composition and fixation procedure (( 10.1002/elps.201000608 )) Strategy for high‐fidelity multiplex DNA copy number assay system using capillary electrophoresis devices (( 10.1002/elps.201100093 )) Electrokinetic particle translocation through a nanopore containing a floating electrode (( 10.1002/elps.201100050 )) Sequential injection setup for capillary isoelectric focusing combined with MS detection (( 10.1002/elps.201100012 ))     

Overview of capillary electrophoresis and capillary electrochromatography.

This paper provides an overview on the current status of capillary electrophoresis (CE) and capillary electrochromatography (CEC). The focus is largely on the current application areas of CE where routine methods are now in place. These application areas include the analysis of DNA, clinical and forensic samples, carbohydrates, inorganic anions and metal ions, pharmaceuticals, enantiomeric species and proteins and peptides. More specific areas such the determination of physical properties, microchip CE and instrumentation developments are also covered. The application, advantages and limitations of CEC are covered. Recent review articles and textbooks are frequently cited to provide readers with a source of information regarding pioneering work and theoretical treatments.     

Cover Picture: Electrophoresis 2'2011

Issue no. 2 is a regular issue assembled of 16 solid and original research articles distributed over 3 distinct parts. Part I is on novel trends in fundamentals and methodologies including theoretical models for selectivity of charged solutes in MEKC, system peaks in indirect detection, measuring epimerization constants by MEEKC, bundled CE using micro‐structured fibers, 2‐D separations by coupling CIEF and CEC, high speed DNA CE, MCE of N‐glycans and mucin expression in a microfluidic gradient device. Part II is concerned with detection, sensitivity enhancement, on‐column preconcentration and microdialysis sampling involving the design of continuous full filling CEC‐ESI‐MS using nanoparticles, CE‐fluorescence using tapered optical fiber, CZE separation of pesticide residues in water samples with acid‐assisted on‐column preconcentration and CE‐LIF to detect neurotransmitter amino acids and carbamathione in brain microdialysis samples. Novel methods for the separation and profiling of various proteins and large nucleic fragments are described in 4 consecutive papers grouped in part III. Featured articles include: Theoretical models of separation selectivity for charged compounds in micellar electrokinetic chromatography (( 10.1002/elps.201000405 )) Bundled capillary electrophoresis using microstructured fibres ( 10.1002/elps.201000442 )) Two‐dimensional separation system by on‐line hyphenation of capillary isoelectric focusing with pressurized capillary electrochromatography for peptide and protein mapping ( 10.1002/elps.201000419 )) Microchip electrophoresis of N‐glycans on serpentine separation channels with asymmetrically tapered turns ( 10.1002/elps.201000461 ))     

Laser‐Induced Fluorometry for Capillary Electrophoresis

Laser‐induced fluorometry (LIF) has achieved the detection of single molecules, which ranks it among the most sensitive of detection techniques, whereas capillary electrophoresis (CE) is known as a powerful separation method with resolution that is beyond the reach of many other types of chromatography. Therefore, a coupling of LIF with CE has established an unrivaled analytical technique in terms of sensitivity and resolution. CE‐LIF has demonstrated excellent performance in bioanalytical chemistry for the high‐resolution separation and highly sensitive detection of DNAs, proteins, and small bioactive molecules. This review describes the CE‐LIF methods developed by the author's group that include indirect and direct detection using diode lasers, post‐column derivatization, and Hadamard transformation, as well as applications to the binding assays of specific DNA immunoassays of proteins and to the determination of anticancer drugs.     

Joule heating and determination of temperature in capillary electrophoresis and capillary electrochromatography columns

This article reviews the progress that has taken place in the past decade on the topic of estimation of Joule heating and temperature inside an open or packed capillary in electro-driven separation techniques of capillary electrophoresis (CE) and capillary electrochromatography (CEC), respectively. Developments in theoretical modeling of the heat transfer in the capillary systems have focused on attempts to apply the existing models on newer techniques such as CEC and chip-based CE. However, the advent of novel analytical tools such as pulsed magnetic field gradient nuclear magnetic resonance (NMR), NMR thermometry, and Raman spectroscopy, have led to a revolution in the area of experimental estimation of Joule heating and temperature inside the capillary via the various noninvasive techniques. This review attempts to capture the major findings that have been reported in the past decade.     

Cover Picture: Electrophoresis 21'2010

Issue no. 21 is a regular issue with "Emphasis on Nucleic Acids" and comprises 17 contributions distributed over 4 distinct parts. Part I is on nucleic acids and has 8 research articles on various aspects of nucleic acid research including an automated instrument for human STR identification, a high resolution chip‐CE assay for rapid detection of gene mutations and amplifications, a fluorescence‐based sequence‐specific primer PCR, pulsed field CE for RNA separation, methylated DNA immunoprecipitation sequencing, PCR‐SSCP, DNA methylation, and analysis of SNPs. Part II has 4 research articles dealing with studies on protein and proteomics analysis, e.g., microchip IEF, CE analysis of microheterogeneous glutelin subunits in rice, protein precipitation methods and prefractionation of plasma for proteomic analysis. Part III has 2 contributions that describe the separation of the enantiomers of DL‐isocitric acid by CE and the analysis of trace degradation products of S‐adenosylmethionine, which are decarboxylated diastereomers, by CE. The last 3 articles in this issue (Part IV) are on novel methodologies for facile interfacing of CE with MS, electrokinetic chromatography for the determination of contaminants and impurities of heparin samples, and particle electrophoresis. As such, issue no. 21 is packed with the latest developments and innovations in the field. Featured articles include: An automated instrument for Human STR identification: design, characterization, and experimental validation (doi: 10.1002/elps.201000305 )) Miniature flowing atmospheric‐pressure afterglow ion source for facile interfacing of capillary electrophoresis with mass spectrometry (doi: 10.1002/elps.201000350 )) Capillary electrophoresis for analysis of microheterogeneous glutelin subunits in rice (Oryza sativa L.). (doi: 10.1002/elps.201000333 ))     

毛细管电泳进样技术新进展

评述了毛细管电泳进样技术新成果。对直接在线进样，二维分离体系中毛细管电泳分离的增样，相关毛细管电泳增样，超微量样品及单个分子的进样，近端进样，双向进样和高温下的进样装置的应用状况作了介绍。     

CE determination of small ions: methods and techniques

This paper provides an overview on the current status of capillary electrophoresis (CE) in the analysis of inorganic and charged small organic species. The various CE strategies used to improve the separation of ionic analytes are summarized. Technical developments in the design of improved detection systems are described. A brief account of their advantages and limitations is given. The potential use of these devices for miniaturized CE systems is also described. Finally, special attention is focused on the on-capillary preconcentration techniques developed in attempts to overcome the poor detectability of CE. Recent review articles are frequently cited to provide readers with a source of information about pioneering work, theoretical treatments, and specific applications.     

Capillary electrophoresis of glucosinolates and their degradation products

Glucosinolates are important natural products occurring mainly in plants of the Cruciferae family. This review article is aimed at describing the recent progress made in capillary electrophoresis of glucosinolates and their degradation products. It describes the various electrophoretic systems and detection schemes introduced to date for the capillary electrophoresis (CE) of glucosinolates and their degradation products. Also included in this review are the applications of CE to the qualitative and quantitative determination of glucosinolates and their degradation products in plant extracts.     

Cover Picture: Electrophoresis 11'2011

Issue no. 11 is a regular issue consisting of 17 contributions distributed over 6 distinct parts: Part I is on fundamentals and methodologies containing 4 research articles dealing with electrokinetic transport through nanochannels, electroosmotic flow in polygonal ducts, analysis of complex samples by mass spectrometry using a sample pretreatment by preparative CITP, and CE analysis of inorganic cations in post‐blast residue extracts; Part II has 5 contributions on various aspects of proteomics and proteins including structural analysis of the recombinant therapeutic product rFVIII, electrophoretic characterization of proteins isolated by various extraction methods from ejaculated and capacitated boar sperms, CE separations of proteins using cationic poly(amidoamine) dendrimers, hemoglobin depletion in erythrocyte cytosolic samples, and peptide fractionation by acid pH SDS‐free electrophoresis; Part III is on separations of malignant cells, and particle capture in a droplet using dielectrophoresis; Part IV has two contributions on CEC separations; Part V consists of two papers on genetic variability and amplification; Part VI is on food analysis with one review article on CE applications in food analysis and one research paper on the determination of betaines in vegetable oils by CE‐MS. Thus, issue no. 11 covers many important subjects. Featured articles include: Electrokinetic transport through nanochannels (( 10.1002/elps.201000564 )) Interdigitated comb‐like electrodes for continuous separation of malignant cells from blood using dielectrophoresis (( 10.1002/elps.201000625 )) Experimental study of dielectrophoresis and liquid dielectrophoresis mechanisms for particle capture in a droplet (( 10.1002/elps.201000548 )) Thirty years of capillary electrophoresis in food analysis laboratories: Potential applications (( 10.1002/elps.201000541 ))     

Cover Picture: Electrophoresis 21'2011

Issue no. 21 is a regular issue consisting of one FAST TRACK article on “Blinded study determination of high sensitivity and specificity microchip electrophoresis‐SSCP/HA to detect mutations in the p53 gene” and 19 other contributions distributed over 5 distinct parts. Part I is on proteins and proteomics containing 5 contributions describing on‐line combination of multiple chromatographic modes for multicomponent separation of proteomics and glycoproteomics, the heterogeneity of plasma‐derived clotting factor VIII, rapid species evaluation of seafood spoilage and pathogenic Gram‐positive bacteria by MALDI‐TOF mass fingerprinting, comparison of depletion and equalization strategies in proteomics, and a competent extraction method for 2‐D gel electrophoresis. Part II is on affinity capillary electrophoresis and has 2 contributions on the application of partial‐filling using lectins and glycosidases for the characterization of oligosaccharides in therapeutic antibodies, and on protonated diamines as anion‐binding agents and their utility in CE separations. 5 contributions on detection and sensitivity enhancement make up the body of Part III. DNA translocation and depurination constitute the content of the two contributions of Part IV. Finally, Part V assembles 5 papers on various fundamentals and methodologies including the influence of membrane layer properties on the electrophoretic behavior of a soft particle, evaluation of the separation mechanism of EKC with microemulsion and CDs using NMR and molecular modeling, linear polyalkylamines as fingerprinting agents in CE of low‐molecular weight heparins and glycosaminoglycans, use of CE‐SDS gel for the characterization of monoclonal antibody hinge region clipping due to copper and high pH stress, and electrophoretic isolation of saponin fractions from Saponinum album and their evaluation in synergistically enhancing the receptor‐specific cytotoxicity of targeted toxins. In short, this regular issue has a myriad of topics, which make the issue a must to read. Featured articles include: FAST TRACK: Blinded study determination of high sensitivity and specificity microchip electrophoresis‐SSCP/HA to detect mutations in the p53 gene (( 10.1002/elps.201100396 )) Online combination of reversed‐phase/reversed‐phase and porous graphitic carbon liquid chromatography for multicomponent separation of proteomics and glycoproteomics samples (( 10.1002/elps.201100092 )) Trace determination of perchlorate using electromembrane extraction and capillary electrophoresis with capacitively coupled contactless conductivity detection (( 10.1002/elps.201100279 )) Sensitivity enhancement in capillary electrophoresis‐mass spectrometry of anionic metabolites using a triethylamine‐containing background electrolyte and sheath liquid (( 10.1002/elps.201100271 )) Evaluation of the separation mechanism of electrokinetic chromatography with a microemulsion and cyclodextrins using NMR and molecular modeling (( 10.1002/elps.201100263 ))