Rukhsana Jabeen 1 Deborah Payne 2 John Wiktorowicz 3 Amin Mohammad 1 John Petersen 1 1 University of Texas Medical Branch – Pathology, Galveston, TX, USA 2 University of Texas Southwestern Medical Center – Pathology, Dallas, TX, USA 3 University of Texas Medical Branch – Biochemistry & Molecular Biology, Galveston, TX, USA Received December 22, 2005 Revised March 14, 2006 Accepted March 14, 2006 Review Capillary electrophoresis and the clinical laboratory Over the past 15 years, CE as an analytical tool has shown great promise in replacing many conventional clinical laboratory methods, such as electrophoresis and HPLC. CE’s appeal was that it was fast, used very small amounts of sample and reagents, was extremely versatile, and was able to separate large and small analytes, whether neutral or charged. Because of this versatility, numerous methods have been developed for analytes that are of clinical interest. Other than molecular diagnostic and forensic laboratories CE has not been able to make a major impact in the United States. In contrast, in Europe and Japan an increasing number of clinical laboratories are using CE. Now that automated multicapillary instruments are commercially available along with cost-effective test kits, CE may yet be accepted as an instrument that will be routinely used in the clinical laboratories. This review will focus on areas where CE has the potential to have the greatest impact on the clinical laboratory. These include analyses of proteins found in serum and urine, hemoglobin (A1c and variants), carbo- hydrate-deficient transferrin, forensic and therapeutic drug screening, and molecular diagnostics. Keywords: Capillary electrophoresis / Clinical applications / Clinical laboratory / Molecular diagnostics DOI 10.1002/elps.200500948 1 Introduction CE is a relatively new separation technology that uses a narrow capillary format with an internal diameter ,100 mm that has multiple benefits for analysis of mole- cules that are of clinical interest. The efficient heat dis- sipation by the narrow format capillaries allows for high electric fields, resulting in rapid separations and increased resolution. It comes as no surprise, however, that these benefits are accompanied by difficulties, including peak collection and low concentrations after collection; low detection sensitivity due to the very narrow diameter of the capillary; severe loss in resolution due to overloading for analytes whose concentrations are high; and the tendency of charged capillary surfaces to create EEO and cause mass transfer of analytes to the capillary walls, also causing severe loss in resolution. Most, if not all, of these difficulties have been overcome by structural or chemical modifications of the capillaries and/or physi- cal modification of instruments. However, the success of a CE analysis still relies on careful consideration of all of these factors. In spite of the problems, the popularity of this technique is a testimonial to its versatility in the range of analytes that can be separated, from small molecule drugs (including neutral species) to proteins and DNA; its speed, usually in minutes; its minuscule sample size requirement, measured in nanoliters; and its reproduci- bility with a relative standard error of migration time gen- erally ,0.5%. As a result, with the introduction of the first commercial instrument in 1989, almost 10 000 papers have been published describing the theory of CE, its instrumenta- tion, and its applications* including its use in the clinical laboratory for the analysis of biological fluids. The fea- tures that appeal to clinical chemists are speed, minimal Correspondence: Dr. John Petersen, University of Texas Medical Branch – Pathology, 301 University Blvd, Galveston, TX 77555- 0551, USA E-mail: jrpeters@utmb.edu Fax: 11-4097729245 Abbreviations: AGE, agarose gel electrophoresis; CAE, cellulose acetate; CAP , College of American Pathologists; CDT , carbohy- drate-deficient transferrins; CF , cystic fibrosis; GHB, g-hydroxybuty- ric acid; HbA1c, glycated hemoglobin; HIV , human immunodefi- ciency virus; LOH, loss of heterozygosity; MC, monoclonal compo- nent; MLPA, multiplex ligase polymerase assay; MRD, minimal residual disease; RT , reverse transcriptase; Tf, transferrin Electrophoresis 2006, 27, 2413–2438 2413  2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.electrophoresis-journal.com