Project Brief
Tools For DNA Diagnostics (July 1995)An Integrated Microelectronic DNA Diagnostic SystemTo speed the entry of cost-effective DNA analysis into the clinical diagnostic laboratory, an integrated system is proposed that will carry out all necessary sample preparation and analytical procedures in a linked series of microfabricated sites that sum into a microlaboratory on a single chip. Sponsor: Nanogen, Inc.10398 Pacific Center CourtSan Diego, CA 92121
If it weren't for the proven feats of the microelectronics industry and its growing offspring technology in the areas of microfabrication and microengineering, the idea of reducing a sophisticated analytical laboratory to the size of a microscope slide would fit into the pie-in-the-sky-category. Nanogen, Inc., proposes to prove this by developing a fully integrated microelectronic system, which can rapidly carry out all aspects of DNA diagnostic analysis. The concept is to design an integrated set of microelectronic components on a single wafer or chip. Each site relies on electronically controlled properties of cells and molecules to achieve separation, selectivity, and identification of medically relevant DNA sequences in samples. A cell selector site will exploit the different binding affinities of different cell types under different electric conditions to select appropriate cells such as white blood cells. The next site on the wafer will rely on the same principle of binding affinity to separate and extract genomic DNA from other biochemical components of the selected cells. Another site will carry out a "crude" preselection of medically relevant DNA regions of a sample by passing the sample DNA over an addressable array of DNA probes, each of which has a sequence associated with a genetic or infectious disease. Finally, a site patterned with multiple wells will analyze in detail each selected sample fragment for specific genetic mutations or patterns. In this analytical site, each addressable well is fitted with a DNA probe that will capture sample DNA only if it harbors culprit DNA sequences. Binding is detected by looking for light from dye molecules designed to intercalate (bundle up) with the complexes that form between a probe and sample DNA. From the pattern of fluorescence, the sequence of the sample DNA can be inferred. Four consultants from universities and one from a microfabrication company will contribute to the project. The ATP award will support the sample preparation portion of the research; other funding sources are supporting the DNA analysis portion.
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