Developments in Interfacing Designs for CE–MS: Towards Enabling Tools for Proteomics and Metabolomics

Abstract

Capillary electrophoresis–mass spectrometry (CE–MS) can be considered a useful analytical technique for the analysis of charged compounds in the fields of proteomics and metabolomics. Currently, the commercially available co-axial sheath–liquid interface is generally employed for coupling CE to MS in most application areas. Although it has proven to be rather robust for various proteomics, glycomics and metabolomics studies, the intrinsically low-flow separation property of CE is not effectively utilized in this set-up. In this type of interfacing the sheath–liquid (typical flow-rate between 1 and 10 µL/min) dilutes the CE effluent (flow-rate between 20 and 100 nL/min), thereby reducing the detection sensitivity. Over the past few years some significant developments that aim to overcome this limitation have been made in interfacing techniques for CE–MS, which resulted in an increased interest of CE–MS for proteomics and metabolomics. This paper provides an overview of these developments and the utility of CE–MS employing the new interfacing techniques is demonstrated by representative examples in the fields of proteomics, glycomics and metabolomics. Finally, general conclusions and perspectives are provided.

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References

  1. 1.

    Kuehnbaum NL, Britz-McKibbin P (2013) Chem Rev 113:2437–2468

    Article  CAS  Google Scholar 

  2. 2.

    Zhao SS, Zhong X, Tie C, Chen DD (2012) Proteomics 12:2991–3012

    Article  CAS  Google Scholar 

  3. 3.

    Haselberg R, de Jong GJ, Somsen GW (2013) Electrophoresis 34:99–112

    Article  CAS  Google Scholar 

  4. 4.

    Ramautar R, Somsen GW, de Jong GJ (2009) Electrophoresis 30:276–291

    Article  CAS  Google Scholar 

  5. 5.

    Herrero M, Ibanez E, Cifuentes A (2008) Electrophoresis 29:2148–2160

    Article  CAS  Google Scholar 

  6. 6.

    Zhao SS, Chen DD (2014) Electrophoresis 35:96–108

    Article  CAS  Google Scholar 

  7. 7.

    Maxwell EJ, Chen DD (2008) Anal Chim Acta 627:25–33

    Article  CAS  Google Scholar 

  8. 8.

    Hommerson P, Khan AM, de Jong GJ, Somsen GW (2011) Mass Spectrom Rev 30:1096–1120

    Article  CAS  Google Scholar 

  9. 9.

    Soga T, Ohashi Y, Ueno Y, Naraoka H, Tomita M, Nishioka T (2003) J Proteome Res 2:488–494

    Article  CAS  Google Scholar 

  10. 10.

    Mischak H, Vlahou A, Ioannidis JP (2013) Clin Biochem 46:432–443

    Article  CAS  Google Scholar 

  11. 11.

    Chalcraft KR, Britz-McKibbin P (2009) Anal Chem 81:307–314

    Article  CAS  Google Scholar 

  12. 12.

    Servais AC, Crommen J, Fillet M (2006) Electrophoresis 27:2616–2629

    Article  CAS  Google Scholar 

  13. 13.

    Mokaddem M, Gareil P, Belgaied JE, Varenne A (2009) Electrophoresis 30:1692–1697

    Article  CAS  Google Scholar 

  14. 14.

    Simpson SL Jr, Quirino JP, Terabe S (2008) J Chromatogr A 1184:504–541

    Article  CAS  Google Scholar 

  15. 15.

    Breadmore MC, Shallan AI, Rabanes HR, Gstoettenmayr D, Abdul Keyon AS, Gaspar A, Dawod M, Quirino JP (2013) Electrophoresis 34:29–54

    Article  CAS  Google Scholar 

  16. 16.

    Ramautar R, Somsen GW, de Jong GJ (2014) Electrophoresis 35:128–137

    Article  CAS  Google Scholar 

  17. 17.

    Kleparnik K (2013) Electrophoresis 34:70–85

    Article  CAS  Google Scholar 

  18. 18.

    Ramautar R, de Jong GJ (2014) Bioanalysis 6:1011–1026

    Article  CAS  Google Scholar 

  19. 19.

    Bonvin G, Schappler J, Rudaz S (2012) J Chromatogr A 1267:17–31

    Article  CAS  Google Scholar 

  20. 20.

    Moini M (2007) Anal Chem 79:4241–4246

    Article  CAS  Google Scholar 

  21. 21.

    Maxwell EJ, Zhong X, Zhang H, van Zeijl N, Chen DD (2010) Electrophoresis 31:1130–1137

    Article  CAS  Google Scholar 

  22. 22.

    Wojcik R, Dada OO, Sadilek M, Dovichi NJ (2010) Rapid Commun Mass Spectrom 24:2554–2560

    Article  CAS  Google Scholar 

  23. 23.

    Wang C, Lee CS, Smith RD, Tang K (2013) Anal Chem 85:7308–7315

    Article  CAS  Google Scholar 

  24. 24.

    Jorgenson JW, Lukacs KD (1981) Clin Chem 27:1551–1553

    CAS  Google Scholar 

  25. 25.

    Huber CG, Hölzl G (2001) Chapter 8 Hyphenation of capillary electrochromatography and mass spectrometry: Instrumental aspects, separation systems, and applications. In: Zdeněk D, Frantiaek V (eds) J Chromatogr Libr, Elsevier, pp. 271–316

  26. 26.

    Reiter SM, Buchberger W, Klampfl C (2010) Chromatographia 71:715–719

    Article  CAS  Google Scholar 

  27. 27.

    Yamashita M, Fenn JB (1984) J Phys Chem Us 88:4451–4459

    Article  CAS  Google Scholar 

  28. 28.

    Aleksandrov ML, Gall LN, Krasnov NV, Nikolaev VI, Pavlenko VA, Shkurov VA, Baram GI, Grachev MA, Knorre VD, Kusner YS (1984) Bioorg Khim 10:710–712

    CAS  Google Scholar 

  29. 29.

    Bruins AP, Covey TR, Henion JD (1987) Anal Chem 59:2642–2646

    Article  CAS  Google Scholar 

  30. 30.

    Huang EC, Wachs T, Conboy JJ, Henion JD (1990) Anal Chem 62:A713

    Google Scholar 

  31. 31.

    Henion JD (2009) Clin Chem 55:1234–1235

    Article  CAS  Google Scholar 

  32. 32.

    Smith RD, Barinaga CJ, Udseth HR (1988) Anal Chem 60:1948–1952

    Article  CAS  Google Scholar 

  33. 33.

    Foret F, Thompson TJ, Vouros P, Karger BL, Gebauer P, Bocek P (1994) Anal Chem 66:4450–4458

    Article  CAS  Google Scholar 

  34. 34.

    Monton MR, Soga T (2007) J Chromatogr A 1168:237–246; discussion 236

    Article  CAS  Google Scholar 

  35. 35.

    Ramautar R, Torano JS, Somsen GW, de Jong GJ (2010) Electrophoresis 31:2319–2327

    Article  CAS  Google Scholar 

  36. 36.

    Sanz-Nebot V, Balaguer E, Benavente F, Barbosa J (2005) Electrophoresis 26:1457–1465

    Article  CAS  Google Scholar 

  37. 37.

    Jantos-Siwy J, Schiffer E, Brand K, Schumann G, Rossing K, Delles C, Mischak H, Metzger J (2009) J Proteome Res 8:268–281

    Article  CAS  Google Scholar 

  38. 38.

    Haselberg R, Ratnayake CK, de Jong GJ, Somsen GW (2010) J Chromatogr A 1217:7605–7611

    Article  CAS  Google Scholar 

  39. 39.

    Causon TJ, Maringer L, Buchberger W, Klampfl CW (2014) J Chromatogr A 1343:182–187

    Article  CAS  Google Scholar 

  40. 40.

    Tie C, Zhang DW, Chen HX, Song SL, Zhang XX (2012) J Mass Spectrom 47:1429–1434

    Article  CAS  Google Scholar 

  41. 41.

    Faserl K, Sarg B, Kremser L, Lindner H (2011) Anal Chem 83:7297–7305

    Article  CAS  Google Scholar 

  42. 42.

    Busnel JM, Schoenmaker B, Ramautar R, Carrasco-Pancorbo A, Ratnayake C, Feitelson JS, Chapman JD, Deelder AM, Mayboroda OA (2010) Anal Chem 82:9476–9483

    Article  CAS  Google Scholar 

  43. 43.

    Ramautar R, Busnel JM, Deelder AM, Mayboroda OA (2012) Anal Chem 84:885–892

    Article  CAS  Google Scholar 

  44. 44.

    Hirayama A, Tomita M, Soga T (2012) Analyst 137:5026–5033

    Article  CAS  Google Scholar 

  45. 45.

    Zhong X, Maxwell EJ, Ratnayake C, Mack S, Chen DD (2011) Anal Chem 83:8748–8755

    Article  CAS  Google Scholar 

  46. 46.

    Zhong X, Maxwell EJ, Chen DD (2011) Anal Chem 83:4916–4923

    Article  CAS  Google Scholar 

  47. 47.

    Lindenburg PW, Ramautar R, Jayo RG, Chen DD, Hankemeier T (2014) Electrophoresis 35:1308–1314

    Article  CAS  Google Scholar 

  48. 48.

    Sun L, Zhu G, Yan X, Champion MM, Dovichi NJ (2014) Proteomics 14:622–628

    Article  CAS  Google Scholar 

  49. 49.

    Li Y, Wojcik R, Dovichi NJ, Champion MM (2012) Anal Chem 84:6116–6121

    Article  CAS  Google Scholar 

  50. 50.

    Wojcik R, Li Y, Maccoss MJ, Dovichi NJ (2012) Talanta 88:324–329

    Article  CAS  Google Scholar 

  51. 51.

    Li Y, Champion MM, Sun L, Champion PA, Wojcik R, Dovichi NJ (2012) Anal Chem 84:1617–1622

    Article  CAS  Google Scholar 

  52. 52.

    Sun L, Zhu G, Zhao Y, Yan X, Mou S, Dovichi NJ (2013) Angew Chem Int Ed Engl 52:13661–13664

    Article  CAS  Google Scholar 

  53. 53.

    Heemskerk AA, Deelder AM, Mayboroda OA (2014) Mass Spectrom Rev

  54. 54.

    Ramautar R, Heemskerk AA, Hensbergen PJ, Deelder AM, Busnel JM, Mayboroda OA (2012) J Proteomics 75:3814–3828

    Article  CAS  Google Scholar 

  55. 55.

    Haselberg R, Oliveira S, van der Meel R, Somsen GW, de Jong GJ (2014) Anal Chim Acta 818:1–6

    Article  CAS  Google Scholar 

  56. 56.

    Haselberg R, de Jong GJ, Somsen GW (2013) Anal Chem 85:2289–2296

    Article  CAS  Google Scholar 

  57. 57.

    Kohler I, Augsburger M, Rudaz S, Schappler J (2014) Forensic Sci Int 243:14–22

    Article  CAS  Google Scholar 

  58. 58.

    Marie A-L, Przybylski C, Gonnet F, Daniel R, Urbain R, Chevreux G, Jorieux S, Taverna M (2013) Anal Chim Acta 800:103–110

    Article  CAS  Google Scholar 

  59. 59.

    Bracke N, Wynendaele E, D’Hondt M, Haselberg R, Somsen GW, Pauwels E, Van de Wiele C, De Spiegeleer B (2014) J Pharm Biomed Anal 96:1–9

    Article  CAS  Google Scholar 

  60. 60.

    Gusenkov S, Ackaert C, Stutz H (2013) Electrophoresis 34:2695–2704

    Article  CAS  Google Scholar 

  61. 61.

    Heukers R, Altintas I, Raghoenath S, De Zan E, Pepermans R, Roovers RC, Haselberg R, Hennink WE, Schiffelers RM, Kok RJ, Van Bergen en Henegouwen PMP (2014) Biomaterials 35:601–610

    Article  CAS  Google Scholar 

  62. 62.

    Li Y, Compton PD, Tran JC, Ntai I, Kelleher NL (2014) Proteomics 14:1158–1164

    Article  Google Scholar 

  63. 63.

    Zhao Y, Sun L, Champion MM, Knierman MD, Dovichi NJ (2014) Anal Chem 86:4873–4878

    Article  CAS  Google Scholar 

  64. 64.

    Sun L, Knierman MD, Zhu G, Dovichi NJ (2013) Anal Chem 85:5989–5995

    Article  CAS  Google Scholar 

  65. 65.

    Sun L, Zhu G, Zhao Y, Yan X, Mou S, Dovichi NJ (2013) Angew Chem Int Ed 52:13661–13664

    Article  CAS  Google Scholar 

  66. 66.

    Zhu G, Sun L, Yan X, Dovichi NJ (2013) Anal Chem 85:2569–2573

    Article  CAS  Google Scholar 

  67. 67.

    Zhu G, Sun L, Yan X, Dovichi NJ (2014) Anal Chem 86:6331–6336

    Article  CAS  Google Scholar 

  68. 68.

    Zhu G, Sun L, Yan X, Dovichi NJ (2014) Anal Chim Acta 810:94–98

    Article  CAS  Google Scholar 

  69. 69.

    Whitmore CD, Gennaro LA (2012) Electrophoresis 33:1550–1556

    Article  CAS  Google Scholar 

  70. 70.

    Gross PC, Burkart SC, Muller R (2014) J Pharm Biomed Anal 88:477–482

    Article  CAS  Google Scholar 

  71. 71.

    Zhu G, Sun L, Linkous T, Kernaghan D, McGivney JB, Dovichi NJ (2014) Electrophoresis 35:1448–1452

    Article  CAS  Google Scholar 

  72. 72.

    Zaia J (2013) Methods Mol Biol 984:13–25

    Article  CAS  Google Scholar 

  73. 73.

    Haselberg R, de Jong GJ, Somsen GW (2013) Anal Chem 85:2289–2296

    Article  CAS  Google Scholar 

  74. 74.

    Maxwell EJ, Ratnayake C, Jayo R, Zhong X, Chen DD (2011) Electrophoresis 32:2161–2166

    Article  CAS  Google Scholar 

  75. 75.

    Jayo RG, Li J, Chen DD (2012) Anal Chem 84:8756–8762

    Article  CAS  Google Scholar 

  76. 76.

    Hirayama A, Wakayama M, Soga T TrAC Trends Analyt Chem

  77. 77.

    Ramautar R, Shyti R, Schoenmaker B, de Groote L, Derks RJ, Ferrari MD, van den Maagdenberg AM, Deelder AM, Mayboroda OA (2012) Anal Bioanal Chem 404:2895–2900

    Article  CAS  Google Scholar 

  78. 78.

    Soliman LC, Hui Y, Hewavitharana AK, Chen DD (2012) J Chromatogr A 1267:162–169

    Article  CAS  Google Scholar 

  79. 79.

    Kok MG, de Jong GJ, Somsen GW (2011) Electrophoresis 32:3016–3024

    Article  CAS  Google Scholar 

  80. 80.

    Yang WC, Regnier FE, Adamec J (2008) Electrophoresis 29:4549–4560

    Article  CAS  Google Scholar 

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Acknowledgments

Dr. Rawi Ramautar would like to acknowledge the financial support of the Veni grant scheme of the Netherlands Organization of Scientific Research (NWO Veni 722.013.008).

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Correspondence to Rawi Ramautar.

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Published in the topical collection Recent Developments in Clinical Omics with guest editors Martin Giera and Manfred Wuhrer.

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Lindenburg, P.W., Haselberg, R., Rozing, G. et al. Developments in Interfacing Designs for CE–MS: Towards Enabling Tools for Proteomics and Metabolomics. Chromatographia 78, 367–377 (2015). https://doi.org/10.1007/s10337-014-2795-5

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Keywords

  • Capillary electrophoresis
  • Mass spectrometry
  • Interfaces
  • Proteomics
  • Metabolomics