SEQUENCING DNA IN NANOFABRICATED ARRAYS

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DESCRIPTION (Adapted from the investigator's abstract): This research proposal is based on the premise that DNA analysis and sequencing is at the heart of all genome projects and most, if not all, research in molecular, cellular, and developmental biology. The investigators point out that this is also fast becoming a major part of modern medical and forensic practice, and such trends in analytical and functional genomics will continue to accelerate for the foreseeable future. Thus, the need for new and different ways to sequence and analyze DNA has long been recognized. The investigators state that current methodologies are relatively slow, they are not very portable, and they often require skilled technical staff, usually concentrated in special units within university, medical and industrial settings. In this application possible solutions to sequencing speed, cost, and portability are proposed. Artificial SiO-based devices in which to concentrate, handle, and analyze small (nl) volumes of sequencing reactions, restriction digests of DNA molecules, and devices capable of resolving and analyzing chromosome-sized DNA are described. The central idea is to exploit advances in the semiconductor industry to fabricate synthetic "gels" on a small (square centimeter) chip. The approach utilizes recent advances in patterning and etching on the nano and micro scale. The investigators point to advantages of the proposed devices, such as speed (less than a minute for many embodiments), low cost (replicas of each device can be made for less than one dollar), and the ease with which they can be designed to run in parallel (many channels).