Sample introduction techniques for microfabricated separation devices.

A great deal of progress has been made toward the development of the micro total analysis system (micro-TAS) since its inception in 1990. A wide variety of applications, including genomics, proteomics and drug discovery, have prompted the development of analytical methods capable of very high throughput while maintaining low cost. The micro-TAS concept addresses both of these requirements. Electrophoresis has been a key element in the development of the micro-TAS. Most chemical and biochemical assays utilize a separation component at some point during analysis. Genomics, in particular, depends almost exclusively on electrophoresis for size-based separations of DNA. This review examines sample introduction into microfabricated electrophoretic devices, or chips, primarily for DNA analysis. Sample introduction is an important component of these systems and is an essential process for making chip electrophoresis a widely applicable analytical technique. Specific issues, such as automation, the delivery of large numbers of samples to microfabricated devices and injection of picoliter-sized sample plugs into a separation lanes on chips, are presented.