Recent developments and applications of capillary and microchip electrophoresis in proteomic and peptidomic analyses.

This review presents recent developments and applications of capillary and microchip electromigration methods in proteomics and peptidomics. Sample preparation methods as well as instrumental innovations in the coupling of these advanced electromigration methods with mass spectrometry detection employed in proteomic and peptidomic analyses are presented. Interesting applications of various capillary electromigration methods in bottom-up as well as top-down proteomics, including investigation of post-translational modifications of proteins are described. In addition, several examples of the use of capillary electromigration methods combined with mass spectrometry detection in clinical proteomics and peptidomics are demonstrated.

[1]  Lorna M. Lopez,et al.  A pilot study of urinary peptides as biomarkers for intelligence in old age , 2011 .

[2]  Bogusław Buszewski,et al.  Two-dimensional gel electrophoresis in the light of new developments , 2014 .

[3]  A. Vlahou,et al.  A comparison between MALDI-MS and CE-MS data for biomarker assessment in chronic kidney diseases. , 2012, Journal of proteomics.

[4]  N. Dovichi,et al.  Fast top-down intact protein characterization with capillary zone electrophoresis-electrospray ionization tandem mass spectrometry. , 2013, Analytical chemistry.

[5]  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.

[6]  H. Mischak,et al.  Recent advances in capillary electrophoresis coupled to mass spectrometry for clinical proteomic applications , 2013, Electrophoresis.

[7]  N. Dovichi,et al.  High sensitivity capillary zone electrophoresis-electrospray ionization-tandem mass spectrometry for the rapid analysis of complex proteomes. , 2013, Current opinion in chemical biology.

[8]  L. Fricker,et al.  Peptidomics: identification and quantification of endogenous peptides in neuroendocrine tissues. , 2006, Mass spectrometry reviews.

[9]  E. Yeung,et al.  Determination of NAD(+) and NADH in a single cell under hydrogen peroxide stress by capillary electrophoresis. , 2009, Analytical chemistry.

[10]  H. Mischak,et al.  Urinary proteomics in obstructive sleep apnoea and obesity , 2014, European journal of clinical investigation.

[11]  E. Guihen.  Recent advances in miniaturization—The role of microchip electrophoresis in clinical analysis , 2014, Electrophoresis.

[12]  P. Finch,et al.  Peptidomics: Bridging the gap between proteome and metabolome , 2006, Proteomics.

[13]  Richard D. Smith,et al.  Mass spectrometry-based proteomics: existing capabilities and future directions. , 2012, Chemical Society reviews.

[14]  Alain Beck,et al.  Analysis of monoclonal antibody by a novel CE‐UV/MALDI‐MS interface , 2014, Electrophoresis.

[15]  Albert Sickmann,et al.  Current strategies and findings in clinically relevant post-translational modification-specific proteomics , 2015, Expert review of proteomics.

[16]  H. Mischak,et al.  Peptide Fingerprinting of Alzheimer's Disease in Cerebrospinal Fluid: Identification and Prospective Evaluation of New Synaptic Biomarkers , 2011, PloS one.

[17]  D. Figeys,et al.  Proteomics: from technology developments to biological applications. , 2009, Analytical chemistry.

[18]  Thierry Rabilloud,et al.  Power and limitations of electrophoretic separations in proteomics strategies. , 2009, Mass spectrometry reviews.

[19]  Jonathan V Sweedler,et al.  Application of capillary electrophoresis for the early diagnosis of cancer , 2014, Analytical and Bioanalytical Chemistry.

[20]  Angelina Taichrib,et al.  Toward a screening method for the analysis of small intact proteins by CE‐ESI‐TOF MS , 2012, Electrophoresis.

[21]  Bing Yu,et al.  Recent progress in preparation and application of microfluidic chip electrophoresis , 2015 .

[22]  James M. Karlinsey.  Sample introduction techniques for microchip electrophoresis: a review. , 2012, Analytica chimica acta.

[23]  High speed capillary zone electrophoresis-mass spectrometry via an electrokinetically pumped sheath flow interface for rapid analysis of amino acids and a protein digest. , 2015, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

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

[25]  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.

[26]  Pier Giorgio Righetti,et al.  Capillary electrophoresis and isoelectric focusing in peptide and protein analysis , 2013, Proteomics.

[27]  David D Y Chen,et al.  Applications of capillary electrophoresis in characterizing recombinant protein therapeutics , 2014, Electrophoresis.

[28]  A. Ganser,et al.  Proteomic peptide profiling for preemptive diagnosis of acute graft-versus-host disease after allogeneic stem cell transplantation , 2013, Leukemia.

[29]  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.

[30]  M. Markuszewski,et al.  Multidimensional capillary electrophoresis , 2015, Electrophoresis.

[31]  N. Kelleher,et al.  Top Down proteomics: facts and perspectives. , 2014, Biochemical and biophysical research communications.

[32]  Leigh Anderson.  Six decades searching for meaning in the proteome. , 2014, Journal of proteomics.

[33]  H. Mischak,et al.  A peptidomic approach to biomarker discovery for bovine mastitis. , 2013, Journal of proteomics.

[34]  V. R. Robledo,et al.  Review of the CE‐MS platform as a powerful alternative to conventional couplings in bio‐omics and target‐based applications , 2014, Electrophoresis.

[35]  W. Xu,et al.  Development and characterizations of a miniature capillary electrophoresis mass spectrometry system. , 2015, Analytical chemistry.

[36]  Andrew G Chambers,et al.  Hybrid capillary/microfluidic system for comprehensive online liquid chromatography-capillary electrophoresis-electrospray ionization-mass spectrometry. , 2013, Analytical chemistry.

[37]  D. D. Chen,et al.  Capillary electrophoresis‐mass spectrometry for analysis of complex samples , 2012, Proteomics.

[38]  A. Gavin,et al.  Quantitative mass spectrometry of posttranslational modifications: Keys to confidence , 2015, Science Signaling.

[39]  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.

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

[41]  A. Hummon,et al.  Proteomic Challenges: Sample Preparation Techniques for Microgram-Quantity Protein Analysis from Biological Samples , 2015, International journal of molecular sciences.

[42]  Karsten Evans,et al.  An integrated microfluidic device for monitoring changes in nitric oxide production in single T-lymphocyte (Jurkat) cells. , 2013, Analytical chemistry.

[43]  R. Kostiainen,et al.  Integration of fully microfabricated, three-dimensionally sharp electrospray ionization tips with microfluidic glass chips. , 2012, Analytical chemistry.

[44]  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.

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

[46]  Xuefei Zhong,et al.  Recent advances in coupling capillary electrophoresis‐based separation techniques to ESI and MALDI‐MS , 2014, Electrophoresis.

[47]  Neil L. Kelleher,et al.  Optimizing capillary electrophoresis for top‐down proteomics of 30–80 kDa proteins , 2014, Proteomics.

[48]  S. Pedersen‐Bjergaard,et al.  The potential of electromembrane extraction for bioanalytical applications. , 2015, Bioanalysis.

[49]  A. Alm,et al.  Proteins in Aqueous Humor from Cataract Patients with and without Pseudoexfoliationsyndrome , 2012, European journal of mass spectrometry.

[50]  R. Kostiainen,et al.  Feasibility of SU‐8‐based capillary electrophoresis‐electrospray ionization mass spectrometry microfluidic chips for the analysis of human cell lysates , 2010, Electrophoresis.

[51]  S. Štěpánová,et al.  Capillary electrophoretic methods applied to the investigation of peptide complexes. , 2015, Journal of separation science.

[52]  A. Heck,et al.  Proteomics beyond trypsin , 2015, The FEBS journal.

[53]  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.

[54]  Yuan-ming Luo,et al.  Interface solution isoelectric focusing with in situ MALDI‐TOF mass spectrometry , 2014, Electrophoresis.

[55]  H. Girault,et al.  High‐sensitive protein analysis by FESI‐CE‐MALDI‐MS , 2011, Electrophoresis.

[56]  J. Ramsey,et al.  High electric field strength two‐dimensional peptide separations using a microfluidic device , 2012, Electrophoresis.

[57]  Amjad Khan,et al.  Ionization techniques in capillary electrophoresis-mass spectrometry: principles, design, and application. , 2011, Mass spectrometry reviews.

[58]  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.

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

[60]  V. Kašička,et al.  Determination of acidity constants and ionic mobilities of polyprotic peptide hormones by CZE , 2013, Electrophoresis.

[61]  J. Pawliszyn,et al.  In vivo and ex vivo SPME: a low invasive sampling and sample preparation tool in clinical bioanalysis. , 2014, Bioanalysis.

[62]  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.

[63]  P. Zürbig,et al.  Use of proteomic methods in the analysis of human body fluids in Alzheimer research , 2012, Electrophoresis.

[64]  H. Husi,et al.  Methods in capillary electrophoresis coupled to mass spectrometry for the identification of clinical proteomic/peptidomic biomarkers in biofluids. , 2015, Methods in molecular biology.

[65]  Chanida Puangpila,et al.  Liquid phase based separation systems for depletion, prefractionation, and enrichment of proteins in biological fluids and matrices for in‐depth proteomics analysis—An update covering the period 2011–2014 , 2015, Electrophoresis.

[66]  Y. Yamini,et al.  Electrical field-induced extraction and separation techniques: promising trends in analytical chemistry--a review. , 2014, Analytica chimica acta.

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

[68]  Julie Klein,et al.  Identification of Urinary Peptide Biomarkers Associated with Rheumatoid Arthritis , 2014, PLoS ONE.

[69]  E. Carrilho,et al.  Homemade Capillary Electrophoresis Coupled to a Mass Spectrometer , 2015 .

[70]  H. V. van Leeuwen,et al.  Capillary-electrophoresis mass spectrometry for the detection of carbapenemases in (multi-)drug-resistant Gram-negative bacteria. , 2014, Analytical chemistry.

[71]  H. Husi,et al.  Classical MALDI-MS versus CE-based ESI-MS proteomic profiling in urine for clinical applications. , 2014, Bioanalysis.

[72]  S. S. Bahga,et al.  Coupling isotachophoresis and capillary electrophoresis: a review and comparison of methods. , 2013, The Analyst.

[73]  Alejandro Cifuentes,et al.  Metabolomics, peptidomics and proteomics applications of capillary electrophoresis-mass spectrometry in Foodomics: a review. , 2013, Analytica chimica acta.

[74]  V. Kašička.  Recent developments in capillary and microchip electroseparations of peptides (2011–2013) , 2014, Electrophoresis.

[75]  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.

[76]  J. Yates,et al.  Protein analysis by shotgun/bottom-up proteomics. , 2013, Chemical reviews.

[77]  Angelina Taichrib,et al.  High resolution TOF MS coupled to CE for the analysis of isotopically resolved intact proteins. , 2011, Journal of proteomics.

[78]  G. Mitulović,et al.  New HPLC Techniques for Proteomics Analysis: A Short Overview of Latest Developments , 2015 .

[79]  H. Mischak,et al.  Comparison of CE‐MS/MS and LC‐MS/MS sequencing demonstrates significant complementarity in natural peptide identification in human urine , 2014, Electrophoresis.

[80]  V. Kašička.  Recent developments in CE and CEC of peptides (2009–2011) , 2012, Electrophoresis.

[81]  Zhaoxiang Zhang,et al.  Recent advances in enhancing the sensitivity and resolution of capillary electrophoresis. , 2013, Journal of chromatographic science.

[82]  N. Kelleher,et al.  Developing top down proteomics to maximize proteome and sequence coverage from cells and tissues. , 2013, Current opinion in chemical biology.

[83]  W. Blackstock,et al.  Proteomics: quantitative and physical mapping of cellular proteins. , 1999, Trends in biotechnology.

[84]  Massimo Castagnola,et al.  Capillary electrophoresis--mass spectrometry: recent trends in clinical proteomics. , 2010, Journal of pharmaceutical and biomedical analysis.

[85]  Fengjun Shang,et al.  Recent advances in miniaturisation – The role of microchip electrophoresis in clinical analysis , 2012, Electrophoresis.

[86]  N. Dovichi,et al.  Integrated capillary zone electrophoresis-electrospray ionization tandem mass spectrometry system with an immobilized trypsin microreactor for online digestion and analysis of picogram amounts of RAW 264.7 cell lysate. , 2013, Analytical chemistry.

[87]  K. Klepárník.  Recent advances in combination of capillary electrophoresis with mass spectrometry: Methodology and theory , 2015, Electrophoresis.

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

[89]  A replaceable microreactor for on-line protein digestion in a two-dimensional capillary electrophoresis system with tandem mass spectrometry detection. , 2011, Journal of chromatography. A.

[90]  R. Longhi,et al.  Quantitative analysis of thymosin β4 in whole saliva by capillary electrophoresis–mass spectrometry using multiple ions monitoring (CE‐MIM‐MS) , 2013, Electrophoresis.

[91]  Jin-Ming Lin,et al.  Recent advances in microchip-mass spectrometry for biological analysis , 2014 .

[92]  S. Camerini,et al.  The role of protein and peptide separation before mass spectrometry analysis in clinical proteomics. , 2015, Journal of chromatography. A.

[93]  H. Mischak,et al.  Urine as a source for clinical proteome analysis: from discovery to clinical application. , 2014, Biochimica et biophysica acta.

[94]  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.

[95]  Govert W Somsen,et al.  CE‐MS for the analysis of intact proteins 2010–2012 , 2013, Electrophoresis.

[96]  Andrea Urbani,et al.  Unraveling the different proteomic platforms. , 2013, Journal of separation science.

[97]  Jin‐Ming Lin,et al.  Recent advances in microfluidics combined with mass spectrometry: technologies and applications. , 2013, Lab on a chip.

[98]  M. Glocker,et al.  Mass spectrometric peptide analysis of 2DE‐separated mouse spinal cord and rat hippocampus proteins suggests an NGxG motif of importance for in vivo deamidation , 2013, Electrophoresis.

[99]  T. Hankemeier,et al.  Lab-on-a-Chip hyphenation with mass spectrometry: strategies for bioanalytical applications. , 2015, Current opinion in biotechnology.

[100]  P. Ferranti,et al.  Proteomics, peptidomics, and immunogenic potential of wheat beer (Weissbier). , 2015, Journal of agricultural and food chemistry.

[101]  T. Janáky,et al.  Challenges and developments in protein identification using mass spectrometry , 2015 .

[102]  B. Koshel,et al.  Trajectory of isoelectric focusing from gels to capillaries to immobilized gradients in capillaries , 2012, Proteomics.

[103]  A. Vlahou,et al.  Clinical applications of capillary electrophoresis coupled to mass spectrometry in biomarker discovery: Focus on bladder cancer , 2013, Proteomics. Clinical applications.

[104]  M. Ward,et al.  Quantitation of protein post-translational modifications using isobaric tandem mass tags. , 2015, Bioanalysis.

[105]  G. D. de Jong,et al.  Low-flow sheathless capillary electrophoresis-mass spectrometry for sensitive glycoform profiling of intact pharmaceutical proteins. , 2013, Analytical chemistry.

[106]  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.

[107]  J. Barbosa,et al.  Modelling the electrophoretic migration behaviour of peptides and glycopeptides from glycoprotein digests in capillary electrophoresis-mass spectrometry. , 2015, Analytica chimica acta.

[108]  S. Lunte,et al.  Recent advances in the analysis of therapeutic proteins by capillary and microchip electrophoresis. , 2014, Analytical methods : advancing methods and applications.

[109]  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.

[110]  D. Lian,et al.  Progress in stacking techniques based on field amplification of capillary electrophoresis , 2014, Analytical and Bioanalytical Chemistry.

[111]  A. Vlahou,et al.  Capillary zone electrophoresis on‐line coupled to mass spectrometry: A perspective application for clinical proteomics , 2015, Proteomics. Clinical applications.

[112]  C. Neusüss,et al.  Capillary electrophoresis in two‐dimensional separation systems: Techniques and applications , 2015, Electrophoresis.

[113]  René P Zahedi,et al.  The next level of complexity: Crosstalk of posttranslational modifications , 2014, Proteomics.

[114]  M. Westphall,et al.  Coupling capillary zone electrophoresis with electron transfer dissociation and activated ion electron transfer dissociation for top-down proteomics. , 2015, Analytical chemistry.

[115]  R. Westermeier.  Looking at proteins from two dimensions: a review on five decades of 2D electrophoresis , 2014, Archives of physiology and biochemistry.

[116]  K. Otsuka,et al.  Recent Progress of On-line Sample Preconcentration Techniques in Microchip Electrophoresis , 2012, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[117]  A. Manz,et al.  Present state of microchip electrophoresis: state of the art and routine applications. , 2015, Journal of chromatography. A.

[118]  K. Otsuka,et al.  Recent applications of on-line sample preconcentration techniques in capillary electrophoresis. , 2014, Journal of chromatography. A.

[119]  N. Dovichi,et al.  Capillary Zone Electrophoresis–Electrospray Ionization-Tandem Mass Spectrometry for Top-Down Characterization of the Mycobacterium marinum Secretome , 2014, Analytical chemistry.

[120]  J. Ramsey,et al.  Monolithic integration of two-dimensional liquid chromatography-capillary electrophoresis and electrospray ionization on a microfluidic device. , 2011, Analytical chemistry.

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

[122]  Anna Bierczynska-Krzysik,et al.  Methods for samples preparation in proteomic research. , 2007, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[123]  G. J. Jong,et al.  Developments in coupled solid‐phase extraction–capillary electrophoresis 2011–2013 , 2014, Electrophoresis.

[124]  C. Lebrilla,et al.  Current peptidomics: Applications, purification, identification, quantification, and functional analysis , 2015, Proteomics.

[125]  J. Barbosa,et al.  Identification of bioactive peptides in hypoallergenic infant milk formulas by CE‐TOF‐MS assisted by semiempirical model of electromigration behavior , 2013, Electrophoresis.

[126]  T. Hankemeier,et al.  Isotachophoretic phenomena in electric field gradient focusing: perspectives for sample preparation and bioassays. , 2014, Analytical chemistry.

[127]  Chun-song Zheng,et al.  CE‐ESI‐MS coupled with dynamic pH junction online concentration for analysis of peptides in human urine samples , 2010, Electrophoresis.

[128]  R. Kostiainen,et al.  Interfacing microchip isoelectric focusing with on-chip electrospray ionization mass spectrometry. , 2015, Journal of chromatography. A.

[129]  P. A. Kler,et al.  Column–coupling strategies for multidimensional electrophoretic separation techniques , 2014, Analytical and Bioanalytical Chemistry.

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

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

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

[133]  A. Capriotti,et al.  Intact protein separation by chromatographic and/or electrophoretic techniques for top-down proteomics. , 2011, Journal of chromatography. A.

[134]  F. Foret,et al.  Capillary electrophoresis in an extended nanospray tip-electrospray as an electrophoretic column. , 2015, Journal of chromatography. A.

[135]  A. deMello,et al.  Affinity chromatography and capillary electrophoresis for analysis of the yeast ribosomal proteins. , 2012, BMB reports.

[136]  B. Sarg,et al.  Comparing and Combining Capillary Electrophoresis Electrospray Ionization Mass Spectrometry and Nano–Liquid Chromatography Electrospray Ionization Mass Spectrometry for the Characterization of Post-translationally Modified Histones , 2013, Molecular & Cellular Proteomics.

[137]  John R Yates,et al.  Capillary electrophoresis applied to proteomic analysis. , 2009, Journal of separation science.