Capillary zone electrophoresis-mass spectrometry for bottom-up proteomics

Abstract Bottom-up proteomics characterizes proteins by analysis of peptides generated through proteolysis. Bottom-up analysis of a complex proteome inevitably generates tens of thousands of peptides, and the analysis of these peptides is a serious challenge. Capillary zone electrophoresis (CZE) generates separations that are orthogonal to reversed phase liquid chromatography, which has led to consideration of CZE as an alternative separation technology in proteomic analysis. The steady improvement in mass spectrometer (MS) technology coupled with improvements in capillary coatings and the development of robust CZE-MS interfaces have contributed to the rapid advancement of CZE's identification performance in bottom-up proteomics analysis. In this review, we focus on recent advances of CZE-MS based bottom-up proteomics, including optimization of CZE and MS conditions, and the application of CZE-MS in phosphoproteomics, glycoproteomics, clinical diagnosis, host cell protein analysis, ultrasensitive proteomics, and quantitative proteomics. Finally, we outline future opportunities and challenges in this field.

[1]  S. Hess,et al.  Effect of mass spectrometric parameters on peptide and protein identification rates for shotgun proteomic experiments on an LTQ‐orbitrap mass analyzer , 2012, Proteomics.

[2]  John R Yates,et al.  The revolution and evolution of shotgun proteomics for large-scale proteome analysis. , 2013, Journal of the American Chemical Society.

[3]  Liangliang Sun,et al.  Over 4100 protein identifications from a Xenopus laevis fertilized egg digest using reversed‐phase chromatographic prefractionation followed by capillary zone electrophoresis–electrospray ionization–tandem mass spectrometry analysis , 2016, Proteomics.

[4]  Liangliang Sun,et al.  Over 10,000 peptide identifications from the HeLa proteome by using single-shot capillary zone electrophoresis combined with tandem mass spectrometry. , 2014, Angewandte Chemie.

[5]  S. Perrier,et al.  'Green' reversible addition-fragmentation chain-transfer (RAFT) polymerization. , 2010, Nature chemistry.

[6]  J. Yates,et al.  Large-scale analysis of the yeast proteome by multidimensional protein identification technology , 2001, Nature Biotechnology.

[7]  Elizabeth H. Peuchen,et al.  Preparation of linear polyacrylamide coating and strong cationic exchange hybrid monolith in a single capillary, and its application as an automated platform for bottom-up proteomics by capillary electrophoresis-mass spectrometry , 2017, Microchimica Acta.

[8]  N. Dovichi,et al.  Accurate determination of peptide phosphorylation stoichiometry via automated diagonal capillary electrophoresis coupled with mass spectrometry: proof of principle. , 2013, Analytical chemistry.

[9]  M. Breadmore,et al.  Online sample pre-concentration via dynamic pH junction in capillary and microchip electrophoresis. , 2011, Journal of separation science.

[10]  Jesse G. Meyer,et al.  Charge State Coalescence During Electrospray Ionization Improves Peptide Identification by Tandem Mass Spectrometry , 2012, Journal of The American Society for Mass Spectrometry.

[11]  G. Vidarsson,et al.  Coupling porous sheathless interface MS with transient‐ITP in neutral capillaries for improved sensitivity in glycopeptide analysis , 2013, Electrophoresis.

[12]  T. D. de Reijke,et al.  An In-Depth Glycosylation Assay for Urinary Prostate-Specific Antigen , 2018, Analytical chemistry.

[13]  N. Dovichi,et al.  Automated enzyme-based diagonal capillary electrophoresis: application to phosphopeptide characterization. , 2010, Analytical chemistry.

[14]  Liangliang Sun,et al.  Capillary zone electrophoresis-mass spectrometry with microliter-scale loading capacity, 140 min separation window and high peak capacity for bottom-up proteomics. , 2017, The Analyst.

[15]  R. Aebersold,et al.  Protein identification by solid phase microextraction—capillary zone electrophoresis—microelectrospray—tandem mass spectrometry , 1996, Nature Biotechnology.

[16]  Cheng-Huang Lin,et al.  On‐line sample concentration techniques in capillary electrophoresis: Velocity gradient techniques and sample concentration techniques for biomolecules , 2004, Electrophoresis.

[17]  W. Cheong,et al.  Open tubular capillary electrochromatography with an N-phenylacrylamide-styrene copolymer-based stationary phase for the separation of anomers of glucose and structural isomers of maltotriose. , 2015, Journal of separation science.

[18]  N. Dovichi,et al.  Integrated strong cation-exchange hybrid monolith coupled with capillary zone electrophoresis and simultaneous dynamic pH junction for large-volume proteomic analysis by mass spectrometry. , 2015, Talanta.

[19]  R. Takigiku,et al.  Online Microreactors/Capillary Electrophoresis/Mass Spectrometry for the Analysis of Proteins and Peptides , 1995 .

[20]  Allison Doerr,et al.  Single-cell proteomics , 2018, Nature Methods.

[21]  D. D. Chen,et al.  Electrospray Ionization Interface Development for Capillary Electrophoresis–Mass Spectrometry , 2016 .

[22]  A. Vlahou,et al.  Urinary CE-MS peptide marker pattern for detection of solid tumors , 2018, Scientific Reports.

[23]  Milos V Novotny,et al.  Recent Advances in the Analysis of Complex Glycoproteins. , 2017, Analytical chemistry.

[24]  Richard B. Keithley,et al.  Capillary isoelectric focusing-tandem mass spectrometry and reversed-phase liquid chromatography-tandem mass spectrometry for quantitative proteomic analysis of differentiating PC12 cells by eight-plex isobaric tags for relative and absolute quantification. , 2013, Analytical chemistry.

[25]  H. Mischak,et al.  CE‐MS in biomarker discovery, validation, and clinical application , 2011, Proteomics. Clinical applications.

[26]  S. Terabe,et al.  On-line sample preconcentration in capillary electrophoresis. Fundamentals and applications. , 2008, Journal of chromatography. A.

[27]  Richard D. Smith,et al.  Combining capillary electrophoresis with mass spectrometry for applications in proteomics , 2005, Electrophoresis.

[28]  N. Dovichi,et al.  Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry as an alternative proteomics platform to ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry for samples of intermediate complexity. , 2012, Analytical chemistry.

[29]  W. Xu,et al.  Recent advances of capillary electrophoresis-mass spectrometry instrumentation and methodology , 2017 .

[30]  John D. Venable,et al.  Comparison of different signal thresholds on data dependent sampling in orbitrap and LTQ mass spectrometry for the identification of peptides and proteins in complex mixtures , 2009, Journal of the American Society for Mass Spectrometry.

[31]  Norman J. Dovichi,et al.  Surface-Confined Aqueous Reversible Addition-Fragmentation Chain Transfer (SCARAFT) Polymerization Method for Preparation of Coated Capillary Leads to over 10 000 Peptides Identified from 25 ng HeLa Digest by Using Capillary Zone Electrophoresis-Tandem Mass Spectrometry. , 2017, Analytical chemistry.

[32]  H. Parving,et al.  Urinary proteomics for prediction of mortality in patients with type 2 diabetes and microalbuminuria , 2018, Cardiovascular Diabetology.

[33]  J. Henion,et al.  Capillary electrophoresis-atmospheric pressure ionization mass spectrometry for the characterization of peptides. Instrumental considerations for mass spectrometric detection. , 1991, Journal of chromatography.

[34]  Albert J R Heck,et al.  Trends in ultrasensitive proteomics. , 2012, Current opinion in chemical biology.

[35]  N. Guzman Biomedical Applications of On-Line Preconcentration-Capillary Electrophoresis Using an Analyte Concentrator: Investigation of Design Options , 1995 .

[36]  C. Lunte,et al.  The Development of a Sheathless Interface for Capillary Electrophoresis Electrospray Ionization Mass Spectrometry Using a Cellulose Acetate Cast Capillary , 2017, Chromatographia.

[37]  J. Gautrot,et al.  Surface-initiated polymer brushes in the biomedical field: applications in membrane science, biosensing, cell culture, regenerative medicine and antibacterial coatings. , 2014, Chemical reviews.

[38]  R. Ramautar,et al.  CE-MS for proteomics: Advances in interface development and application. , 2012, Journal of proteomics.

[39]  Catherine E Costello,et al.  Microfluidic Capillary Electrophoresis-Mass Spectrometry for Analysis of Monosaccharides, Oligosaccharides, and Glycopeptides. , 2017, Analytical chemistry.

[40]  N. Dovichi,et al.  Optimization of mass spectrometric parameters improve the identification performance of capillary zone electrophoresis for single-shot bottom-up proteomics analysis. , 2018, Analytica chimica acta.

[41]  Lingjun Li,et al.  Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry for Quantitative Analysis of Glycans Labeled with Multiplex Carbonyl-Reactive Tandem Mass Tags. , 2015, Analytical chemistry.

[42]  Evgenia Shishkova,et al.  Now, More Than Ever, Proteomics Needs Better Chromatography. , 2016, Cell systems.

[43]  N. Dovichi,et al.  Bottom-Up Proteomics of Escherichia coli Using Dynamic pH Junction Preconcentration and Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry , 2014, Analytical chemistry.

[44]  M. Girolami,et al.  Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease* , 2010, Molecular & Cellular Proteomics.

[45]  John R Yates,et al.  Mass spectrometry in high-throughput proteomics: ready for the big time , 2010, Nature Methods.

[46]  Liangliang Sun,et al.  Absolute quantitation of host cell proteins in recombinant human monoclonal antibodies with an automated CZE‐ESI‐MS/MS system , 2014, Electrophoresis.

[47]  Z. Shihabi,et al.  Stacking in capillary zone electrophoresis. , 2000, Journal of chromatography. A.

[48]  F. Galeotti,et al.  Recent advances in capillary electrophoresis separation of monosaccharides, oligosaccharides, and polysaccharides , 2018, Electrophoresis.

[49]  Laura Sola,et al.  Enhancing Proteomic Throughput in Capillary Electrophoresis–Mass Spectrometry by Sequential Sample Injection , 2017, Proteomics.

[50]  W. Cheong,et al.  High Efficiency Robust Open Tubular Capillary Electrochromatography Column for the Separation of Peptides , 2016 .

[51]  R. Cole,et al.  Cetyltrimethylammonium chloride as a surfactant buffer additive for reversed-polarity capillary electrophoresis-electrospray mass spectrometry. , 1993, Journal of chromatography. A.

[52]  Ruedi Aebersold,et al.  Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry , 2003, Nature Biotechnology.

[53]  P. Iadarola,et al.  Recent applications of CE‐ and HPLC‐MS in the analysis of human fluids , 2016, Electrophoresis.

[54]  K. Klepárník,et al.  Recent advances in CE‐MS coupling: Instrumentation, methodology, and applications , 2017, Electrophoresis.

[55]  Liangliang Sun,et al.  Capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry for quantitative parallel reaction monitoring of peptide abundance and single-shot proteomic analysis of a human cell line. , 2014, Journal of chromatography. A.

[56]  Liangliang Sun,et al.  Strong cation exchange-reversed phase liquid chromatography-capillary zone electrophoresis-tandem mass spectrometry platform with high peak capacity for deep bottom-up proteomics. , 2018, Analytica chimica acta.

[57]  W. Cheong,et al.  Open tubular capillary column for the separation of cytochrome C tryptic digest in capillary electrochromatography. , 2015, Journal of separation science.

[58]  J. Yates,et al.  Identification of proteins in complexes by solid-phase microextraction/multistep elution/capillary electrophoresis/tandem mass spectrometry. , 1999, Analytical chemistry.

[59]  Václav Kašička,et al.  Recent developments and applications of capillary and microchip electrophoresis in proteomic and peptidomic analyses. , 2016, Journal of separation science.

[60]  Richard D. Smith,et al.  Ultrasensitive sample quantitation via selected reaction monitoring using CITP/CZE-ESI-triple quadrupole MS. , 2012, Analytical Chemistry.

[61]  J. Barbosa,et al.  Capillary electrophoresis time-of-flight mass spectrometry for a confident elucidation of a glycopeptide map of recombinant human erythropoietin. , 2011, Rapid communications in mass spectrometry : RCM.

[62]  N. Dovichi,et al.  Site-Specific Glycan Heterogeneity Characterization by Hydrophilic Interaction Liquid Chromatography Solid-Phase Extraction, Reversed-Phase Liquid Chromatography Fractionation, and Capillary Zone Electrophoresis-Electrospray Ionization-Tandem Mass Spectrometry. , 2018, Analytical chemistry.

[63]  T. Hankemeier,et al.  Simple capillary electrophoresis-mass spectrometry method for complex glycan analysis using a flow-through microvial interface. , 2014, Analytical chemistry.

[64]  Richard D. Smith,et al.  Capillary zone electrophoresis-MS , 1988, Nature.

[65]  Serge Rudaz,et al.  Capillary electrophoresis-electrospray ionization-mass spectrometry interfaces: fundamental concepts and technical developments. , 2012, Journal of chromatography. A.

[66]  H. Lindner,et al.  Quantitative Proteomics Using Ultralow Flow Capillary Electrophoresis–Mass Spectrometry , 2015, Analytical chemistry.

[67]  P. Vouros,et al.  Peer Reviewed: Advances in CE/MS. , 1999 .

[68]  R Apweiler,et al.  On the frequency of protein glycosylation, as deduced from analysis of the SWISS-PROT database. , 1999, Biochimica et biophysica acta.

[69]  F. Foret,et al.  On‐line CE/ESI/MS interfacing: Recent developments and applications in proteomics , 2012, Proteomics.

[70]  Peter K. Sorger,et al.  Measuring and Modeling Apoptosis in Single Cells , 2011, Cell.

[71]  R. Aebersold,et al.  Protein identification by capillary zone electrophoresis/microelectrospray ionization-tandem mass spectrometry at the subfemtomole level. , 1996, Analytical chemistry.

[72]  O. Mayboroda,et al.  Sialic acid linkage differentiation of glycopeptides using capillary electrophoresis – electrospray ionization – mass spectrometry , 2017, Scientific Reports.

[73]  A. Vlahou,et al.  CE‐MS‐based proteomics in biomarker discovery and clinical application , 2015, Proteomics. Clinical applications.

[74]  Yanyan Qu,et al.  Production of Over 27 000 Peptide and Nearly 4400 Protein Identifications by Single-Shot Capillary-Zone Electrophoresis-Mass Spectrometry via Combination of a Very-Low-Electroosmosis Coated Capillary, a Third-Generation Electrokinetically-Pumped Sheath-Flow Nanospray Interface, an Orbitrap Fusion Lu , 2018, Analytical chemistry.

[75]  D. Muddiman,et al.  Factorial Experimental Designs Elucidate Significant Variables Affecting Data Acquisition on a Quadrupole Orbitrap Mass Spectrometer , 2013, Journal of The American Society for Mass Spectrometry.

[76]  N. Dovichi,et al.  Predicting Electrophoretic Mobility of Tryptic Peptides for High-Throughput CZE-MS Analysis. , 2017, Analytical chemistry.

[77]  Thomas L. Fillmore,et al.  Capillary Electrophoresis-Nanoelectrospray Ionization-Selected Reaction Monitoring Mass Spectrometry via a True Sheathless Metal-Coated Emitter Interface for Robust and High-Sensitivity Sample Quantification. , 2016, Analytical chemistry.

[78]  N. Dovichi,et al.  Thermally-initiated free radical polymerization for reproducible production of stable linear polyacrylamide coated capillaries, and their application to proteomic analysis using capillary zone electrophoresis-mass spectrometry. , 2016, Talanta.

[79]  M. MacCoss,et al.  Capillary electrophoresis with Orbitrap-Velos mass spectrometry detection. , 2012, Talanta.

[80]  John R Yates,et al.  Proteomics by mass spectrometry: approaches, advances, and applications. , 2009, Annual review of biomedical engineering.

[81]  B. Sarg,et al.  Investigating capillary electrophoresis‐mass spectrometry for the analysis of common post‐translational modifications , 2018, Electrophoresis.

[82]  N. Dovichi,et al.  Multisegment injections improve peptide identification rates in capillary zone electrophoresis-based bottom-up proteomics. , 2017, Journal of chromatography. A.

[83]  R. Aebersold,et al.  Mass spectrometry-based proteomics , 2003, Nature.

[84]  W. D. Braddock,et al.  Preliminary investigations of preconcentration-capillary electrophoresis-mass spectrometry. , 1995, Journal of chromatography. B, Biomedical applications.

[85]  R. Aebersold,et al.  High‐sensitivity determination of tyrosine‐phosphorylated peptides by on‐line enzyme reactor and electrospray ionization mass spectrometry , 1995, Protein science : a publication of the Protein Society.

[86]  Harald Mischak,et al.  Capillary electrophoresis coupled to mass spectrometry for clinical diagnostic purposes , 2005, Electrophoresis.

[87]  Liangliang Sun,et al.  Third-generation electrokinetically pumped sheath-flow nanospray interface with improved stability and sensitivity for automated capillary zone electrophoresis-mass spectrometry analysis of complex proteome digests. , 2015, Journal of proteome research.

[88]  Ruedi Aebersold,et al.  Mass-spectrometric exploration of proteome structure and function , 2016, Nature.

[89]  Nicholas W. Kwiecien,et al.  Improved Precursor Characterization for Data-Dependent Mass Spectrometry. , 2018, Analytical chemistry.

[90]  Liangliang Sun,et al.  Deep Top-Down Proteomics Using Capillary Zone Electrophoresis-Tandem Mass Spectrometry: Identification of 5700 Proteoforms from the Escherichia coli Proteome. , 2018, Analytical chemistry.

[91]  Shaorong Liu,et al.  Cross-linked polyacrylamide coating for capillary isoelectric focusing. , 2004, Analytical chemistry.

[92]  E. Yeung,et al.  Optimization of selectivity in capillary zone electrophoresis via dynamic pH gradient and dynamic flow gradient , 1992 .

[93]  J. Barbosa,et al.  Lowering the concentration limits of detection by on-line solid-phase extraction-capillary electrophoresis-electrospray mass spectrometry. , 2007, Journal of chromatography. A.

[94]  J. Barbosa,et al.  Analysis of recombinant human erythropoietin glycopeptides by capillary electrophoresis electrospray-time of flight-mass spectrometry. , 2012, Analytica chimica acta.

[95]  Rawi Ramautar,et al.  Developments in Interfacing Designs for CE–MS: Towards Enabling Tools for Proteomics and Metabolomics , 2015, Chromatographia.

[96]  Peter Nemes,et al.  Enhanced Peptide Detection Toward Single-Neuron Proteomics by Reversed-Phase Fractionation Capillary Electrophoresis Mass Spectrometry , 2018, Journal of The American Society for Mass Spectrometry.

[97]  Pei-Lun Tsai,et al.  A Brief Review of Bioinformatics Tools for Glycosylation Analysis by Mass Spectrometry. , 2017, Mass spectrometry.

[98]  R. MacIsaac,et al.  Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy , 2012, Diabetes.

[99]  N. Dovichi,et al.  Coupling immobilized alkaline phosphatase-based automated diagonal capillary electrophoresis to tandem mass spectrometry for phosphopeptide analysis. , 2013, Talanta.

[100]  P. Thibault,et al.  Improvement in detection limits for the determination of paralytic shellfish poisoning toxins in shellfish tissues using capillary electrophoresis/electrospray mass spectrometry and discontinuous buffer systems , 1994 .

[101]  Rawi Ramautar,et al.  High capacity capillary electrophoresis-electrospray ionization mass spectrometry: coupling a porous sheathless interface with transient-isotachophoresis. , 2010, Analytical chemistry.

[102]  J. Yates,et al.  Improving the comprehensiveness and sensitivity of sheathless capillary electrophoresis-tandem mass spectrometry for proteomic analysis. , 2012, Analytical chemistry.

[103]  Ronald J. Moore,et al.  Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells , 2018, Nature Communications.

[104]  N. Dovichi,et al.  Comprehensive analysis of host cell impurities in monoclonal antibodies with improved sensitivity by capillary zone electrophoresis mass spectrometry , 2017, Electrophoresis.

[105]  H. Mischak,et al.  Urinary peptidomics in kidney disease and drug research , 2018, Expert opinion on drug discovery.

[106]  M. Novotny,et al.  Capillary electrophoresis-mass spectrometry for direct structural identification of serum N-glycans. , 2017, Journal of chromatography. A.

[107]  R. Dean,et al.  Improving Proteome Coverage on a LTQ-Orbitrap Using Design of Experiments , 2011, Journal of the American Society for Mass Spectrometry.

[108]  Harm-Anton Klok,et al.  Polymer brushes via surface-initiated controlled radical polymerization: synthesis, characterization, properties, and applications. , 2009, Chemical reviews.

[109]  A. Pandey,et al.  Assessment of resolution parameters for CID-based shotgun proteomic experiments on the LTQ-Orbitrap mass spectrometer , 2010, Journal of the American Society for Mass Spectrometry.

[110]  Liangliang Sun,et al.  Over 2300 phosphorylated peptide identifications with single-shot capillary zone electrophoresis-tandem mass spectrometry in a 100 min separation. , 2015, Analytical chemistry.

[111]  N. Dovichi,et al.  Dynamic pH junction preconcentration in capillary electrophoresis- electrospray ionization-mass spectrometry for proteomics analysis. , 2016, The Analyst.

[112]  N. Dovichi,et al.  Quantitative multiple reaction monitoring of peptide abundance introduced via a capillary zone electrophoresis-electrospray interface. , 2012, Analytical chemistry.

[113]  H. Mischak,et al.  Capillary electrophoresis–mass spectrometry in urinary proteome analysis: current applications and future developments , 2009, Analytical and bioanalytical chemistry.

[114]  N. Dovichi,et al.  Capillary zone electrophoresis for bottom‐up analysis of complex proteomes , 2016, Proteomics.

[115]  H. Mischak,et al.  Urinary peptide-based classifier CKD273: towards clinical application in chronic kidney disease , 2017, Clinical kidney journal.

[116]  Joseph Zaia,et al.  Mass spectrometry and glycomics. , 2010, Omics : a journal of integrative biology.

[117]  L. Holland,et al.  Capillary Electrophoresis Separations of Glycans , 2018, Chemical reviews.

[118]  Cheng S. Lee,et al.  Recent advances in capillary separations for proteomics , 2004, Electrophoresis.

[119]  S. Perrier,et al.  Bioapplications of RAFT polymerization. , 2009, Chemical reviews.

[120]  Liangliang Sun,et al.  Single-shot proteomics using capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry with production of more than 1250 Escherichia coli peptide identifications in a 50 min separation. , 2013, Analytical chemistry.

[121]  Jesper V Olsen,et al.  Rapid and deep proteomes by faster sequencing on a benchtop quadrupole ultra-high-field Orbitrap mass spectrometer. , 2014, Journal of proteome research.

[122]  K. Matyjaszewski,et al.  Photoinduced Atom Transfer Radical Polymerization with ppm-Level Cu Catalyst by Visible Light in Aqueous Media. , 2015, Journal of the American Chemical Society.

[123]  J. Banks,et al.  Optimization of conditions for the analysis of a peptide mixture and a tryptic digest of cytochrome c by capillary electrophoresis-electrospray-ionization mass spectrometry with an improved liquid-sheath probe , 1995 .

[124]  Richard D. Smith,et al.  On-line mass spectrometric detection for capillary zone electrophoresis , 1987 .

[125]  B. Sarg,et al.  Optimization and evaluation of a sheathless capillary electrophoresis-electrospray ionization mass spectrometry platform for peptide analysis: comparison to liquid chromatography-electrospray ionization mass spectrometry. , 2011, Analytical chemistry.

[126]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[127]  N. Dovichi,et al.  Simplified capillary electrophoresis nanospray sheath-flow interface for high efficiency and sensitive peptide analysis. , 2010, Rapid communications in mass spectrometry : RCM.

[128]  Elizabeth H. Peuchen,et al.  Sensitive and fast characterization of site-specific protein glycosylation with capillary electrophoresis coupled to mass spectrometry. , 2018, Talanta.

[129]  Q. Fang,et al.  A robust and extendable sheath flow interface with minimal dead volume for coupling CE with ESI-MS. , 2018, Talanta.

[130]  B. Balgley,et al.  Recent advances in capillary electrophoresis‐based proteomic techniques for biomarker discovery , 2009, Electrophoresis.

[131]  M. Wirth,et al.  Surface-confined living radical polymerization for coatings in capillary electrophoresis. , 1998, Analytical chemistry.

[132]  Stellan Hjertén,et al.  High-performance electrophoresis : Elimination of electroendosmosis and solute adsorption , 1985 .

[133]  Liangliang Sun,et al.  Capillary zone electrophoresis for analysis of complex proteomes using an electrokinetically pumped sheath flow nanospray interface , 2014, Proteomics.

[134]  N. Dovichi,et al.  Nearly 1000 Protein Identifications from 50 ng of Xenopus laevis Zygote Homogenate Using Online Sample Preparation on a Strong Cation Exchange Monolith Based Microreactor Coupled with Capillary Zone Electrophoresis. , 2016, Analytical chemistry.

[135]  Richard D. Smith,et al.  Capillary isotachophoresis-nanoelectrospray ionization-selected reaction monitoring MS via a novel sheathless interface for high sensitivity sample quantification. , 2013, Analytical chemistry.

[136]  E. Lutz,et al.  Transient isotachophoresis for sensitivity enhancement in capillary electrophoresis‐mass spectrometry for peptide analysis , 2000, Electrophoresis.

[137]  M. Moini Simplifying CE-MS operation. 2. Interfacing low-flow separation techniques to mass spectrometry using a porous tip. , 2007, Analytical chemistry.

[138]  P. Britz‐McKibbin,et al.  Selective focusing of catecholamines and weakly acidic compounds by capillary electrophoresis using a dynamic pH junction. , 2000, Analytical chemistry.

[139]  Peter Nemes,et al.  Tapered-Tip Capillary Electrophoresis Nano-Electrospray Ionization Mass Spectrometry for Ultrasensitive Proteomics: the Mouse Cortex , 2017, Journal of The American Society for Mass Spectrometry.

[140]  N. Dovichi,et al.  Capillary zone electrophoresis as a tool for bottom-up protein analysis. , 2016, Bioanalysis.

[141]  H. Mischak,et al.  Biomarker discovery by CE‐MS enables sequence analysis via MS/MS with platform‐independent separation , 2006, Electrophoresis.

[142]  A. Heck,et al.  Glycoproteomics: A Balance between High-Throughput and In-Depth Analysis. , 2017, Trends in biotechnology.

[143]  Peter Nemes,et al.  Single‐Cell Mass Spectrometry for Discovery Proteomics: Quantifying Translational Cell Heterogeneity in the 16‐Cell Frog (Xenopus) Embryo , 2016, Angewandte Chemie.

[144]  P. Thibault,et al.  Comparison of liquid-junction and coaxial interfaces for capillary electrophoresis-mass spectrometry with application to compounds of concern to the aquaculture industry. , 1992, Journal of chromatography.

[145]  R. Aebersold,et al.  Analysis of dilute peptide samples by capillary zone electrophoresis. , 1990, Journal of chromatography.

[146]  Jian Shen,et al.  Surface-initiated RAFT polymerization of sulfobetaine from cellulose membranes to improve hemocompatibility and antibiofouling property , 2013 .

[147]  E. Maxwell,et al.  Twenty years of interface development for capillary electrophoresis-electrospray ionization-mass spectrometry. , 2008, Analytica chimica acta.

[148]  C. Lucy,et al.  A simple means of generating pH gradients in capillary zone electrophoresis , 1997 .

[149]  Petr Boček,et al.  Stacking phenomena in electromigration: From basic principles to practical procedures , 2003, Electrophoresis.

[150]  Liangliang Sun,et al.  Ultrasensitive and fast bottom-up analysis of femtogram amounts of complex proteome digests. , 2013, Angewandte Chemie.

[151]  O. Mayboroda,et al.  Dopant Enriched Nitrogen Gas Combined with Sheathless Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry for Improved Sensitivity and Repeatability in Glycopeptide Analysis. , 2016, Analytical chemistry.

[152]  Anren Hu,et al.  Using capillary electrophoresis-selective tandem mass spectrometry to identify pathogens in clinical samples. , 2006, Analytical chemistry.

[153]  L. Deterding,et al.  Determination of bioactive peptides using capillary zone electrophoresis/mass spectrometry. , 1991, Analytical chemistry.

[154]  T. Veenstra,et al.  A sheathless nanoflow electrospray interface for on-line capillary electrophoresis mass spectrometry. , 2003, Analytical chemistry.

[155]  V. Sanz-Nebot,et al.  Low-picomolar analysis of peptides by on-line coupling of fritless solid-phase extraction to sheathless capillary electrophoresis-mass spectrometry. , 2014, Journal of chromatography. A.

[156]  Nicolle H Packer,et al.  Advances in LC-MS/MS-based glycoproteomics: getting closer to system-wide site-specific mapping of the N- and O-glycoproteome. , 2014, Biochimica et biophysica acta.

[157]  H. Lingeman,et al.  Comparison between transient isotachophoretic capillary zone electrophoresis and reversed‐phase liquid chromatography for the determination of peptides in plasma , 1999, Electrophoresis.

[158]  N. Dovichi,et al.  Detachable strong cation exchange monolith, integrated with capillary zone electrophoresis and coupled with pH gradient elution, produces improved sensitivity and numbers of peptide identifications during bottom-up analysis of complex proteomes. , 2015, Analytical chemistry.

[159]  N. Dovichi,et al.  Bottom‐up proteome analysis of E. coli using capillary zone electrophoresis‐tandem mass spectrometry with an electrokinetic sheath‐flow electrospray interface , 2013, Proteomics.

[160]  S. Gygi,et al.  Mass spectrometry and proteomics. , 2000, Current opinion in chemical biology.