Capillary electrophoresis miniaturization

A number of developments have increased the importance of capillary electrophoretic methods relative to pumped column methods in analysis. Interactions of analytes with the capillary wall are better understood, inspiring the development of means to minimize wall effects. Capillary electrophoresis (CE) has been standardized to the point of being useful as a routine technique. Incremental improvements in column coating techniques, buffer preparation, and injection techniques, combined with substantive advances in miniaturization and detection have potentiated rugged operation and high capacity massive parallelism in analysis. 

Miniaturized columns have provided a decisive advantage in speed. Uracil, phenol, and benzyl alcohol were separated in 20 seconds by CEC in an 18 mm column with a propyl reversed phase.29 A19 cm electrophoretic channel was etched into a glass wafer, filled with a y-cyclodextrin buffer, and used to resolve chiral amino acids from a meteorite in 4 minutes.30 A 6 cm channel equipped with a syringe pump to automate sample derivatization was used to separate amino acids modified with fluorescein isothiocyanate.31 Nanovials have been used to perform tryptic digests on the 15 nL scale for subsequent separation on capillary Electrophoresis.32 A microcolumn has also been used to generate fractions representing time-points of digestion from a 40 pL sample.33 A disposable nanoelectrospray emitter has been... 

Capillary electrochromatography (CEC) is a miniaturized separation technique that combines aspects of both interactive chromatography and capillary electrophoresis. In this chapter, the theory of CEC and the factors affecting separation such as the stationary phase and mobile phase parameters have been discussed. The chapter focuses on the types and preparation of columns for CEC and describes the progress made in the development of open-tubular, particle-packed, and monolithic columns. The detection techniques in CEC such as the traditional UV detection and improvements made in coupling with more sensitive detectors such as mass spectrometry are also described. The chapter provides a summary of some applications of CEC in the analysis of pharmaceuticals and biotechnology products. 

Manz, A., Harrison, D. J., Verpoorte, E. M. J., Fettinger, J. C., Paulus, A., Luedi, H., and Widmer, H. M. (1992). Planar chips technology for miniaturization and integration of separation techniques into monitoring systems. Capillary electrophoresis on a chip.. Chromatogr. 593, 253-258. 

One drawback of capillary electrophoresis is the state of the capillary wall. Often, constituents of the buffer or analyte are absorbed on the sin-face, causing not only an irreproducible shift of EOF, but even the possibility of questionable binding isotherms. A lot of effort has gone into overcoming this problem. Capillaries with coated inner walls are now commercially available and capillary electrophoresis on chips of different materials is also under development now. Not only do these chips represent a miniaturized form of capillary electrophoresis, but this technique also enables the incorporation of such sample preparation steps as preconcentration and even PCR and immobilization of immunoreagents. It is not difficult to anticipate a very exciting development in this field, one with a high commercial impact. 

G. Chen, L. Zhang and J. Wang, Miniaturized capillary electrophoresis system with a carbon nanotube microelectrode for rapid separation and detection of thiols, Talanta, 64 (2004) 1018-1023. 

The discovery of semiconductor integrated circuits by Bardeen, Brattain, Shockley, Kilby, and Noyce was a revolution in the micro and nano worlds. The concept of miniaturization and integration has been exploited in many areas with remarkable achievements in computers and information technology. The utility of microchips was also realized by analytical scientists and has been used in chromatography and capillary electrophoresis. In 1990, Manz et al. [1] used microfluidic devices in separation science. Later on, other scientists also worked with these units for separation and identification of various compounds. A proliferation of papers has been reported since 1990 and today a good number of publications are available in the literature on NLC and NCE. We have searched the literature through analytical and chemical abstracts, Medline, Science Finder, and peer reviewed journals and found a few thousand papers on chips but we selected only those papers related to NLC and NCE techniques. Attempts have been made to record the development of microfluidic devices in separation science. The number of papers published in the last decade (1998-2007) is shown in Fig. 10.1, which clearly indicates rapid development in microfluidic devices as analytical tools. About 30 papers were published in 1998 that number has risen to 400 in... 

Keywords Miniaturization, integration, microcolumn separations, capillary electrophoresis. 

Campana, A.M.G., Baeyens, W.R.G., Aboul-Enein, H.Y., Zhang, X., Miniaturization of capillary electrophoresis system using micromachining techniques. J. Microcolumn Separations 1998, 10(4), 339-355. 

Harrison, D.J., Fluri, K., Seiler, K., Fan, Z., Effenhauser, C.S., Manz, A., Micro-machining a miniaturized capillary electrophoresis-based chemical analysis system on a chip. Science 1993, 261, 895-897. 

Liu, J., Yan, J., Yang, X., Wang, E., Miniaturized tris(2,2 -bipyiidyl)ruthenium(II) electrochemiluminescence detection cell for capillary electrophoresis and flow injection analysis. Anal. Chem. 2003, 75, 3637-3642. 

Successful extension of the various HPLC detection schemes to capillary electrophoresis has generally involved miniaturizing existing technology while striving for improved sensitivity. 

Some argue that miniaturized tools for both chemical synthesis and analysis need to be integrated onto a single chip to gain the true benefits of miniaturization [57], not least because of the problems associated with subsystem interconnectivity, dead volumes and chip-to-world interfaces. Demonstrations toward such a goal include, for example, a hyphenated mixing reaction channel coupled to a capillary electrophoresis column [58]. 

Other extensions that have been made include the construction of a biochip in which a reverse transcription PCRprocess can be carried out [384] and the integration of PCR with capillary electrophoresis [385], DNA microarray hybridization [386] and sample preparation [387,388]. The speed of analysis, the ease of integrating different functions and the relative low costs of micro-PCR production are important advantages of the miniaturized PCR technique that suggest that this bioorganic microreactor device will be thoroughly implemented in many analytical labs. 

In traditional analytical chemistry the determination of enantiomeric purity is sometimes carried out by capillary electrophoresis (CE) in which the electrolyte contains chiral selectors such as cyclodextrin (CD) derivatives [54], Unfortunately the conventional form of this analytical technique allows only a few dozen ee determinations per day. However, as a consequence of the analytical demands arising from the Human Genome Project, CE has been revolutionized in recent years so that efficient techniques for instrumental miniaturization are now available, making ultra-high-through-put analysis of biomolecules possible for the first time [55]. Two different approaches have emerged, namely capillary array electrophoresis (CAE) [55a - e] and CE on microchips (also called CAE on chips) [55f - m[. Both techniques can be used to carry out... 

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