Modular Ultrahigh Lane Density DNA Sequencing

Improving the speed and efficiency of DNA sequencing methods is essential to the success of the Human Genome Program and to the success of many biotechnology companies such as CuraGen. DNA sequencing remains the rate determining step in much of genetic research. Our goal (and the subject of this proposal) is to dramatically increase the speed and efficiency of gel electrophoresis sequencing using fluorescently tagged DNA. We will investigate the upper throughput bounds of this method by (1) increasing optical format and efficiency, (2) massively increasing the lane density and, hence, the number of samples per run, and (3) improving data handling efficiency through software and dye coding strategies. Sensitivity and throughput increases of 20 fold each may be realized through implementation of optical improvements and a new separation technique. The optical spectroscopy, computation, mathematics, engineering and molecular biology backgrounds present at CuraGen combine with a strong consulting base to put us in a unique position to conceive and carry out this effort. If successful, the instrumental advances achieved in Phase I will be developed into a Phase II prototype. The Phase II prototype will be capable of accepting standard 96 well microtitration plates directly and have an immense commercial advantage over existing systems.