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Clinical applications of capillary electrophoresis

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Abstract

Capillary electrophoresis (CE) is an extremely sensitive technique, which has been used in the clinical laboratory for almost 10 yr. The components of CE instrumentation are described, as are injection modes, buffers, and effects of electroosmotic flow. The modes of separation used in CE, namely, capillary zone electrophoresis, capillary isoelectric focusing, capillary isotachophoresis, and micellar electrokinetic capillary chromatography, are explained. References for 26 different clinical applications of CE are included, among them assays that are used routinely as well as niche assays for specialized applications of CE. Verification of CE assays, current instrumentation, and future development of CE in the clinical laboratory are addressed.

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References

  1. Tiselius, A. (1937) A new apparatus for electrophoretic analysis of colloidal mixtures. Trans. Faraday Soc. 33, 524–536.

    Article  CAS  Google Scholar 

  2. Hjerten, S. (1990) Zone broadening in electrophoresis with special reference to high-performance electrophoresis in capillaries: An interplay between theory and practice. Electrophoresis 11, 665–690.

    Article  PubMed  CAS  Google Scholar 

  3. Gordon, M. J., Huang, X., Pentoney, S. L. Jr. and Zare, R. N. (1988) Capillary Electrophoresis. Science 242, 224–228.

    Article  CAS  Google Scholar 

  4. Deyl, Z. and Struzinsky, R. (1991) Review Capillary zone electrophoresis: its applicability and potential in biochemical analysis. J. Chromatogr. 569, 63–122.

    Article  PubMed  CAS  Google Scholar 

  5. Kuhr, W. G. (1990) Capillary Electrophoresis. Anal. Chem., 62, 403R-413R.

    Article  CAS  Google Scholar 

  6. Mazzeo, J. R. and Krull, I. S. (1991) Review Coated capillaries and Additives for the Separations of Proteins by Capillary Zone Electrophoresis and Capillary Isoelectric Focusing. BioTechniques. 10, 638–645.

    PubMed  CAS  Google Scholar 

  7. Shihabi, Z. K. (1992) Clinical Applications of Capillary Electrophoresis. Annals of Clin.and Lab. Science, 22, 398–405.

    CAS  Google Scholar 

  8. Jenkins, M.A. and Guerin, M.D. (1996) Review Capillary Electrophoresis as a Clinical Tool. J. Chromatogr., B. 682, 23–34.

    Article  CAS  Google Scholar 

  9. Lehmann, R., Liebich, H. M. and Voelter, W. (1996) Application of capillary electrophoresis in clinical chemistry — Developments from preliminary trials to routine analysis. J. Cap. Elect. 3, 89–110.

    CAS  Google Scholar 

  10. Perrett, D. (1999) Capillary electrophoresis in clinical chemistry. Ann Clin Biochem 36, 133–150.

    PubMed  CAS  Google Scholar 

  11. Landers, J. P. (ed) (1997) Capillary electrophoresis in the clinical sciences. Electrophoresis 18, 1709–1905.

    Google Scholar 

  12. Krstulovic, A. M. (ed) (1997) Capillary electrophoresis in the life sciences. J. Chromatogr. B. 697, 1–293.

    Google Scholar 

  13. Schwartz, H. E., Ulfelder, K. J., Chen, F-T. A. and Pentoeny, S. L. Jr. (1994) The utility of laser-induced fluorescence detection in applications of capillary electrophoresis. J. Cap. Elect., 3, 89–110.

    Google Scholar 

  14. Oda, R. P., and Landers, J. P. (1996) Introduction, in Capillary Electrophoresis (Landers, J. P. ed.), CRC Press, Boca Raton, USA, pp 1–47.

    Google Scholar 

  15. McLaughlin, G. M., Nolan, J. A., Lindahl, J. L., Palmiere, R. H., Anderson, K. W., Morris, S. C., Morrison, J. A. and Bronzert, T. J. (1992) Pharmaceutical Drug Separations by HPCE: Practical Guidelines, J. Liq. Chromatogr., 15, (6 & 7), 961–1021.

    Article  CAS  Google Scholar 

  16. Zhu, M., Rodriguez R., Hansen, D. and Wehr, T. (1990) Capillary electrophoresis of proteins under alkaline conditions. J. Chromatogr., 516, 123–131.

    Article  PubMed  CAS  Google Scholar 

  17. El Rassi, Z. (1993) Capillary Electrophoresis Overview (Theory and Injection) Printed notes from Workshop at 1993 Frederick Conference on Capillary Electrophoresis.

  18. Cornell, F. N. and McLachlan, R. (1985) Isoelectric Focusing in the Investigation of Gammopathies, in The Clinical Biochemist Monograph (Biegler, B. ed.), The Australian Association of Clinical Biochemists, Perth, pp 31–37.

    Google Scholar 

  19. Chen, S-M. and Wiktorowicz, J. E. (1992) Isoelectric Focusing by Free Solution Capillary Electrophoresis. Anal.Biochem., 206, 84–90.

    Article  PubMed  CAS  Google Scholar 

  20. Chen, S-M. and Wiktorowicz, J. E. (1993) High Resolution Full Range (pI=2.5 to 10.0) Isoelectric Focusing of Proteins and Peptides in Capillary Electrophoresis, in Techniques in Protein Chemistry 1V (Villafranca, J.J. Ed), Academic Press, San Diego, pp333.

    Google Scholar 

  21. Zhu, M., Hansen, D. L., Burd, S., and Gannon, F. (1989) Factors Affecting Free Zone Electrophoresis and Isoelectric Focusing in Capillary Electrophoresis. J. Chromatogr., 480, 311–319.

    Article  CAS  Google Scholar 

  22. Wu, J. and Pawliszyn, J. (1993) Fast analysis of proteins by isoelectric focusing performed in capillary array detected with concentrated gradient imaging system. Electrophoresis, 14, 469–474.

    Article  PubMed  CAS  Google Scholar 

  23. Zhu, M., Wehr, T., Levi, V., Rodriguez, R., Shiffer, K. and Cao, Z.A. (1993) Capillary electrophoresis of abnormal haemoglobins associated with alphathalassemias. J. Chromatogr., A 652, 119–129.

    Article  Google Scholar 

  24. Zhu, M., Rodriguez, R., Wehr, T. and Siebert, C. (1992) Capillary electrophoresis of haemoglobins and globin chains. J. Chromatogr., 608, 225–237.

    Article  PubMed  CAS  Google Scholar 

  25. Rodriguez, R., Zhu, M., Wehr, T. and Siebert, C. (1994) Gravity mobilization of proteins in capillary isoelectricfocusing. Presented at the Sixth International Symposium on High Performance capillary electrophoresis, San Diego, CA., USA.

  26. Jenkins, M. A. and Ratnaike, S. (1999) Capillary isoelectric focusing of haemoglobin variants in the clinical laboratory. Clinica Chimica Acta. 289, 121–132.

    Article  CAS  Google Scholar 

  27. Foret, F., Szoko, E. and Karger, B. L. (1993) Trace analysis of proteins by capillary zone electrophoresis with on-column isotachophoretic preconcentration. Electrophoresis, 14, 417–428.

    Article  PubMed  CAS  Google Scholar 

  28. Terabe, S., Otsuka, K., Ichikawa, K., Tjuchiya, A. and Ando, T. (1984) Electrophoretic separations with micellar solutions and open tubular capillaries. Anal. Chem., 56, 111–113.

    Article  CAS  Google Scholar 

  29. Jenkins, M. A., Kulinskaya, E., Martin, H. D. and Guerin, M. D. (1995) Evaluation of serum protein separation by capillary electrophoresis: prospective analysis of 1000 specimens. J. Chromatogr., B 672, 241–251.

    Google Scholar 

  30. Jenkins, M. A. and Guerin, M. D. (1995) Quantification of serum proteins using capillary electrophoresis. Ann. Clin. Biochem. 32, 493–497.

    PubMed  CAS  Google Scholar 

  31. Jenkins, M. A. and Guerin, M. D. (1996) Optimization of Serum Protein Separation by Capillary Electrophoresis. Clin. Chem., 42, 1886.

    PubMed  CAS  Google Scholar 

  32. Katzmann, J.A., Clark, R., Wiegert, E., Sanders, E., Oda, R. P., Kyle, R. A., Namyst-Goldberg, C. and Landers, J. P. (1997) Identification of monoclonal proteins in serum: A quantitative comparison of acetate, agarose gel, and capillary electrophoresis. Electrophoresis. 18, 1775–1780.

    Article  PubMed  CAS  Google Scholar 

  33. Khatter, N., Ashby, D., Alter, S., Mindeman, L., Kim, H., Wang, J., Liu, J. and Blessum, C. (1993) Identification of monoclonal components by immunosubtraction and capillary electrophoresis. Clin. Chem. 39, 1136.

    Google Scholar 

  34. Bienvenu, J., Graziani, M. S., Arpin, F., Bernon, H., Blessum, C., Marchetti, C., et al. (1998) Multicenter evaluation of the Paragon CZE 2000 capillary zone electrophoresis system for serum protein electrophoresis and monoclonal component typing. Clin. Chem. 44, 599–605.

    PubMed  CAS  Google Scholar 

  35. Henskens, Y., de Winter, J., Pekelharing, M and Ponjee, G. (1998) Detection and identification of monoclonal gammopathies by capillary electrophoresis. Clin. Chem. 44, 1184–1190.

    PubMed  CAS  Google Scholar 

  36. Palfrey, S.M. (1999) Immunosubtraction as a means of typing monoclonal and other proteins in serum and urine, in Clinical applications of capillary electrophoresis (Palfrey, S.M. ed) pp 39–46.

  37. Hempe, J. M. and Craver, R. D. (1994) Quantification of Haemoglobin Variants by Capillary Isoelectric Focusing. Clin. Chem., 40, 2288–2295.

    PubMed  CAS  Google Scholar 

  38. Hempe, J. M., Granger, J. N. and Craver, R. D. (1997) Capillary isoelectric focusing of haemoglobin variants in the pediatric clinical laboratory. Electrophoresis, 18, 1785–1795.

    Article  PubMed  CAS  Google Scholar 

  39. Jenkins, M. A., Hendy, J. and Smith, I. L. (1997) Evaluation of hemoglobin A2 quantitation assay and hemoglobin variant screening by capillary electrophoresis. J. Cap. Elec. 4, 137–143.

    CAS  Google Scholar 

  40. Jenkins, M. A. (1997) Clinical application of capillary electrophoresis to unconcentrated human urine proteins. Electrophoresis. 18, 1842–1846.

    Article  PubMed  CAS  Google Scholar 

  41. Jenkins, M. A., O’Leary, T. D. and Guerin, M. D. (1994) Identification and quantitation of human urine proteins by capillary electrophoresis. J. Chromatogr., B 662, 108–112.

    Google Scholar 

  42. Friedberg, M. A. and Shihabi, Z.K. (1997) Urine protein analysis by capillary electrophoresis. Electrophoresis. 18, 1836–1841.

    Article  PubMed  CAS  Google Scholar 

  43. Houlihan, C., Jenkins, M., Osicka, T., Scott, A., Parkin, D. and Jerums, G. (1999) A comparison of the plasma disappearance of iohexol and 99mTc-DTPA for the measurement of glomerular fiiltration rate (GFR) in diabetes. Aust NZ J Med. 29, 693–700.

    CAS  Google Scholar 

  44. Jenkins, M. A., Houlihan, C., Ratnaike, S., Jerums, G. and Parkin, J. D. (2000) Measurement of iohexol by capillary electrophoresis: minimizing practical problems encountered. Ann Clin. Biochem. (In Press).

  45. Bergert, J. H., Liedtke, R. R., Oda, R. P., Landers, J. P. and Wilson, D.M. (1997) Development of a nonisotopic capillary electrophoresis-based method for measuring glomerular filtration rate. 18, 1827–1835.

    CAS  Google Scholar 

  46. Kobold, U., Jeppsson, J-O., Dulffer, T., Finke, A., Hoelzel, W. and Miedema, K. (1997) Candidate reference methods for hemoglobin A1c based on peptide mapping. Clin. Chem. 43, 1944–1951.

    PubMed  CAS  Google Scholar 

  47. Gelfi, C., Cossu, G., Carta, P., Serra, M. and Righetti, P. G. (1995) Gene dosage in capillary electrophoresis: pre-natal diagnosis of Down’s syndrome. J. Chromatogr., A 718 (2), 405–412.

    Article  Google Scholar 

  48. Righetti, P. G., Gelfi, C. and Cossu, G. F. (1999) Gene dosage in capillary electrophoresis: prenatal diagnosis of Down’s syndrome and Rh D/d genotyping, in Clinical applications of capillary electrophoresis (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp. 109–120.

    Chapter  Google Scholar 

  49. Gross, M., Gathof, B. S., Kolle, P. and Gresser, U. (1995) Capillary electrophoresis for screening of adenylosuccinate lyase deficiency. Electrophoresis 16 (10), 1927–1929.

    Article  PubMed  CAS  Google Scholar 

  50. Oto, M., Suehiro, T. and Yuasa, Y. (1995) Identification of Mutated p53 in Cancer by Non-Gel-Sieving Capillary Electrophoretic SSCP Analysis. Clin. Chem., 41, 1787–1788.

    PubMed  CAS  Google Scholar 

  51. Yu, Z., Scheer, D. and Hempe, J. M. (1999) Quantification of Human Cytomegalovirus by competitive PCR and capillary electrophoresis, in Clinical applications of capillary electrophoresis. (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp 65–80.

    Chapter  Google Scholar 

  52. Kilar, F. and Hjerten, S. (1989) Fast and high resolution analysis of human serum transferrin by high performance isoelectric focusing in capillaries. Electrophoresis 10, 23–29.

    Article  PubMed  CAS  Google Scholar 

  53. Kilar, F. and Hjerten, S. Unfolding of human serum transferrin in urea studied by high-performance capillary electrophoresis. J. Chromatogr. 638, 269–276.

  54. Tagliaro, F., Crivellenye, F., Manetto, G., Puppi, I., Deyl, Z. and Marigo, M. (1998) Optimized determination of carbohydrate-deficient transferrin isoforms in serum by capillary zone electrophoresis. Electrophoresis 19, 3033–3039.

    Article  PubMed  CAS  Google Scholar 

  55. Prasad, R., Stout, R. L., Coffin, D. and Smith, J. (1997) Analysis of carbohydrate deficient transferrin by capillary zone electrophoresis. Electrophoresis 18, 1814–1818.

    Article  PubMed  CAS  Google Scholar 

  56. Arndt T., Hackler R., Kleine T.O. and Gressner A.M. (1998) Validation by isoelectric focusing of the anion-exchange isotransferrin fractionation step involved in determination of carbohydrate-deficient transferrin by the CDTect assay. Clin. Chem. 44, 27–34.

    PubMed  CAS  Google Scholar 

  57. Shirao, M, Furuta, R, Suzuki, S, Nakazawa, H, Fujita, S and Maruyama T. (1994) Determination of organic acids in urine by capillary zone electrophoresis. J. Chromatogr. A. 680, 247–251.

    Article  PubMed  CAS  Google Scholar 

  58. Jariego, C.M. and Hernanz, A. (1996) Determination of Organic Acids by Capillary Electrophoresis in Screening of Organic Acidurias. Clin. Chem., 42, 477–478.

    PubMed  CAS  Google Scholar 

  59. Garcia A., Barbas C., Aguilar R. and Castro M. (1998) Capillary electrophoresis for rapid profiling of organic acidurias. Clin. Chem. 44, 1905–1911.

    PubMed  CAS  Google Scholar 

  60. Marsh, D. B., and Nuttall, K. L. (1995) Methylmalonic acid in clinical urine specimens by capillary zone electrophoresis using indirect photometric detection. J. Cap. Elect. 2, 63–67.

    CAS  Google Scholar 

  61. Schneede, J. and Ueland, P.M. (1995) Application of capillary electrophoresis with laser-induced fluorescence detection for routine determination of methylmalonic acid in human serum. Anal Chem. 67, 812–819.

    Article  PubMed  CAS  Google Scholar 

  62. Ueda, T., Maekawa, T., Sadamitsu, D., Oshita, S., Ogino, K. and Nakamura, K. (1995) The determination of nitrite and nitrate in human blood plasma by capillary zone electrophoresis. Electrophoresis 16 (6), 1002–1004.

    Article  PubMed  CAS  Google Scholar 

  63. Hu, A. Z., Cruzado, I. D., Hill, J. W., McNeal, C. J. and Macfarlane, R. D. (1995) Characterization of lipoprotein a by capillary zone electrophoresis. J. Chromatogr., A 717(1–2), 33–39

    Article  Google Scholar 

  64. Schmitz, G., Mollers, C. and Richter, V. (1997) Analytical capillary isotachophoresis of human serum lipoproteins. Electrophoresis. 18, 1807–1813.

    Article  PubMed  CAS  Google Scholar 

  65. Koay E.S.C., Zhu M., Wehr T., Choong M.L., Khaw M.C., Sethi S.K. and Aw T.C. (1998) Detection of apolipoprotein E genotypes by capillary electrophoresis. Talanta 45, 673–681.

    Article  CAS  Google Scholar 

  66. Watkins, L. K., Cockrill, S. L. and Macfarlane, R. D. (1999) Serum apolipoproteins, in Clinical Applications of Capillary Electrophoresis. (Palfrey, S. M., ed.) Humana, Totowa, NJ, pp 99–108.

    Chapter  Google Scholar 

  67. Holmes, R. P. (1995) Measurement of Urinary Oxalate and Citrate by Capillary Electrophoresis and Indirect Ultraviolet Absorbance. Clin. Chem., 41, 1297–1301.

    PubMed  CAS  Google Scholar 

  68. Holmes, R. P. and Kennedy, M. (1999) Urinary Oxalate and Citrate, in Clinical Applications of Capillary Electrophoresis (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp 199–202.

    Chapter  Google Scholar 

  69. Wildman, B. J., Jackson, P. E., Jones, W. R. and Alden, P. G. (1991) Analysis of anion constituents of urine by inorganic capillary electrophoresis. J. Chromatogr. 546, 459–466.

    Article  PubMed  CAS  Google Scholar 

  70. Jones, W. R. and Jandik, P. (1991) Controlled changes of selectivity in the separation of ions by capillary electrophoresis. J. Chromatogr. 546, 445–458.

    Article  CAS  Google Scholar 

  71. Palfrey, S.M. (1999) Confirmation of the presence of drugs of abuse in urine, in Clinical Applications of Capillary Electrophoresis (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp 165–175.

    Chapter  Google Scholar 

  72. Shihabi, Z. K. (1996) Analysis and general classification of serum cryoglobulins by capillary zone electrophoresis. Electrophoresis. 17 (10), 1607–1612.

    Article  PubMed  CAS  Google Scholar 

  73. Cowdrey, G., Firth, M. and Firth, G. (1995) Separation of cerebrospinal fluid proteins using capillary electrophoresis: A potential method for the diagnosis of neurological disorders. Electrophoresis, 16, 1922–1926.

    Article  PubMed  CAS  Google Scholar 

  74. Cowdrey, G., Firth, M. and Firth, G. (1999) Electrophoresis of cerebrospinal fluid, in Clinical applications of capillary electrophoresis (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp 29–37.

    Chapter  Google Scholar 

  75. Nielsen, R. G., Rickard, E. C., Santa, P. F., Sharknas, D. A. and Sittampalam, G. S. J. (1991) Separation of antibody-antigen complexes by capillary zone electrophoresis, isoelectroc focusing and high-performance size-exclusion chromatography. J. Chromatogr. 539, 177–185.

    Article  PubMed  CAS  Google Scholar 

  76. Schultz, N. M., Huang, L. and Kennedy, R. T. (1995) Capillary electrophoresis-based immunoassay to determine insulin content and insulin secretion from single islets of Langerhans. Anal. Chem. 67, 924–9.

    Article  PubMed  CAS  Google Scholar 

  77. Shimura, K. and Karger, B.L. (1994) Affinity probe capillary electrophoresis: analysis of recombinant human growth hormone with a fluorescent labeled antibody fragment. Anal. Chem. 66, 9–15.

    Article  PubMed  CAS  Google Scholar 

  78. Conti, M., Gelfi C., Bosisio, A. B. and Righetti, P. G. (1996) Quantitation of glycated hemoglobins in human adult blood by capillary isoelectric focusing. Electrophoresis 17, 1590–1596.

    Article  PubMed  CAS  Google Scholar 

  79. Doelman, C. J. A., Siebelder, C. W. M., Nijhof, W. A., Weykamp, C. W., Janssens, J. and Penders, T. J. (1997) Capillary electrophoresis system for haemoglobin A1c determinations evaluated. Clin. Chem., 43, 644–648.

    PubMed  CAS  Google Scholar 

  80. Shihabi, Z. K. and Oles, K. S. (1994) Felbamate measured in serum by two methods: HPLC and capillary electrophoresis. Clin. Chem., 40, 1904–1908.

    PubMed  CAS  Google Scholar 

  81. Abubaker, M. A., Bissell M. G. and Petersen, J. R. (1995) Micellar Electrokinetic Capillary Chromatography to Separate Steroids That Are Increased in Congenital Adrenal Hyperplasia. Clin. Chem., 41, 1369–1370.

    CAS  Google Scholar 

  82. Rao L.V., Petersen J.R., Bissell M.G., Okorodudu A.O. and Mohammad A.A. (1997) Specific determination of urinary free cortisol by solid-phase microparticle extraction capillary electrophoresis with fused silica capillaries. Clin.Chem. 43, 1801–1803.

    PubMed  CAS  Google Scholar 

  83. Shihabi, Z.K. (1999) Enzyme analysis: Cathepsin D as an example, in Clinical applications of capillary electrophoresis (Palfrey, S.M., ed.) Humana, Totowa, NJ, pp 59–64.

    Chapter  Google Scholar 

  84. Beckman Bulletin 9051. Paragon CZE 2000, 1996.

  85. Bio-Rad Bulletin 1955 Rev B.

  86. Beckman Bulletin B96-2552-CB.

  87. Hewlett Packard Publication Number 12-5966-2033E.

  88. Le H., Fung D.C.Y., Yu B. and Trent R.J. (1998) Capillary electrophoresis: new technology for DNA diagnostics. Pathology 30, 304–308.

    Article  PubMed  CAS  Google Scholar 

  89. Guzman N.A., Park S.S., Schaufelberger D., Hernandez L., Paez X., Rada P., Tomlinson A.J. and Naylor S. (1997) Review. New approaches in clinical chemistry: on-line analyte concentration and microreaction capillary electrophoresis for the determination of drugs, metabolic intermediates, and biopolymers in biological fluids. J. Chromatogr. B. 697, 37–66.

    Article  Google Scholar 

  90. Munro, N.J., Snow, K., Kant, J.A. and Landers, J.P. (1999) Molecular diagnostics on microfabricated electrophoretic devices: from slab gel- to Capillary-to Microchip-based assays for T- and B-Cell lymphoproliferative disorders. Clin. Chem. 45, 1906–1917.

    PubMed  CAS  Google Scholar 

  91. Chiem N.H. and Harrison D.J. (1998) Microchip systems for immunoassay: an integrated immunoreactor with electrophoretic separation for serum theophylline determination. Clin Chem 44, 591–598.

    PubMed  CAS  Google Scholar 

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Jenkins, M.A. Clinical applications of capillary electrophoresis. Mol Biotechnol 15, 201–209 (2000). https://doi.org/10.1385/MB:15:3:201

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