This proposal focuses on the development of microfabricated devices to separate and analyze chromosome-size DNA molecules. It will exploit the experience gained in the microelectronics industry for the microfabrication of Si-based devices. The facilities and expertise now exist for the design and manufacture, on a large scale, of microstructures that can be used for the analysis, quantification, and separation of molecules whose molecular weights range in size from a few thousand to many millions of base pairs. An understanding of DNA electrophoresis is of great theoretical and practical importance. Current methods are limited to the separation, in a reasonable time frame, of molecules no larger than 10-7 base pairs. The reasons for this are partially understood, but much remains to be done of both a practical and theoretical nature. This proposal suggests experiments designed to deepen our understanding of theory while creating small scale devices capable of separating molecules this size and larger in hours rather than weeks. Because the devices are two dimensional, many of the problems associated with studying polymers in three dimensions are circumvented. Because they can be manufactured cheaply on a large scale by taking advantage of techniques well established in the solid state industry, they are practical and do not create large quantities of spent chemicals.
