7


Figure 7. Caliper chips


analyser called the Paragon but Sebia have come to dominate this clinical market place. Their Capillaries-2 multi capillary system is designed to fit into the clinical laboratory’s work flow offering pre-made buffer kits etc, is simple to operate and comes with considerable interpretation software. In addition other kits for urinary proteins, haemoglobins and immuno-subtraction are available.


Although multiple capillary CE is commonplace in high throughput genomics very few manufacturers developed such systems for the chemical and pharmaceutical analysis market probably considering the market to be too limited. An Imperial College (London, UK) spin-out company (DeltaDot (London, UK)) entered the CE market place a few years ago employing a novel detection algorithm with a conventional design of CE system. Agilent and Beckman continue to operate in the CE field and seeing the increased use of CE by biotechnology companies they both replaced their long standing instruments with new improved models last year. These systems have improved electronics, a small foot print and better detection modes with enhanced sensitivity.


Lab on a chip.


Miniaturised separations on chip-type devices date back to 1975 when a GC on a chip was constructed at Stanford University. Electrophoresis along with electrokinetic injection revolutionised on-chip analytical devices. Micro-machined electrophoresis probably originated in the very innovative analytical group led by Michael Widmer working in the Swiss pharmaceutical company, Ciba Giegy. In 1992 they described planar glass chip technology for miniaturization and integration of separation techniques into monitoring systems - Capillary electrophoresis on a chip . Over the next decade many other groups both in academia and in various small


companies developed the lab-on-a-chip concept. Devices that incorporated electrolyte loading, voltage control, sample introduction, separation and detection on a single chip were patented and then described with increasing frequency. Initially the chips used acid etched channels on glass slides but chips using more sophisticated soft lithographic techniques able to create increasing complex channels soon became commonplace. Detection usually used laser induced fluorescence since it was difficult to focus other light sources onto the narrow separation channels. Electrochemical detectors have also been employed. Plastic materials e.g. PMMA, polycarbonate, were soon being investigated to fabricate the chips. These chips were easier and cheaper to fabricate. Recently flexible films such as polyester and even paper have been investigated in potentially cheap disposable


Conclusion


Since many molecules carry an intrinsic charge electrophoretic methods will continue to be very important especially in the area of biological analyses. CE is at present undergoing something of a revival in the biotechnology field for protein analysis and to some extent for the chiral analysis of small pharmaceuticals. More systems based on lab- on-chip principles will be developed especially with respect to point of care testing in hospitals and doctors surgeries. In other areas there are hidden applications of electrophoresis e.g. immobility mass spectrometry was developed decades ago as electrophoresis in the gas phase. Yet for many biological laboratories slab gels being simple, cheap and flexible will continue to be a work- horse method for years to come.


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Figure 8. Agilent bioanalyser 2100


devices for say point-of-care (POC) testing in GP surgeries. However most of these chip devices were characterised by a very small chip surrounded by large power supplies and laser beams usually has large or even larger than a standard CE system. The dream of a commercial complete POC system the size of a laptop still appears some way off and the ultimate goal of a mobile phone sized device is even further away. Nevertheless commercial electrophoresis on a chip systems have been around for some time., The Agilent Bioanalyzer when launched in 1999 was the first commercially available instrument to use chip technology for the analysis of DNA and RNA as well as being able to perform SDS- PAGE electrophoresis in a bench-top system. Other companies have entered this market with for example Caliper Life Sciences (Runcorn,UK) offering probably the largest range of instruments including as well as DNA, RNA and protein sizing systems, automated enzyme assays (Kinases) for drug discovery. The current status of electrophoresis on a chip has been reviewed by Arora et al.25


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[20] L. Alfazema, M. Hows, S.Howells D. Perrett Electrophoresis 18 (1997)1047


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[23] J. Zhang, N. J. Dovichi, Agnew Chem Int Ed 39 (2000) 4463


[24] A. Manz. D.J. Harrison, E.M. J, Verpoorte, J. C., Fettinger, A. Paulus, H. Ludi, H.M. Widmer, J Chromatogr 593, (1992) 253


[25] A. Arora, G Simone, G.B. Salieb-Beugelaar, J.T.Kim, A. Manz Anal. Chem., 82 (2010), 4830


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