In this proposal, the investigators introduce new concepts that should make the sequencing of individual DNA fragments by fluorescently identifying individual base pairs a more practical reality. The investigators propose new integrated optical and fluid flow control devices for use in continuous flow sequencing. They will improve delivery of the laser excitation to fluorescently labeled DNA nucleotides with an optical waveguide integrated into the same substrate as a capillary structure in which the fluid flow is confined. This waveguide confines the laser beam to a well-defined, propagation path within the substrate and enables the realization of extremely small (sub-femtoliter) interaction volumes. This waveguide-capillary structure is suitable for the detection of extremely minute quantities of fluorophors down to a single molecule. Beam confinement in the waveguide is similar to confinement in silica optical fibers although in their realization a rectangular ridge waveguide is used. By using planar processing nanofabrication techniques, submicrometer lengths and subfemtoliter volumes are accessible. In the system, all molecules in the flow are constrained to pass through the interaction volume. The integrated structure should have several advantages over published methods of single molecule detection in flowing liquids. With this pilot program, the investigators will develop the concepts leading to a new type of robust high speed sequencing device, with several orders of magnitude higher sequencing rates than present techniques.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HG001519-02
Application #
2674248
Study Section
Special Emphasis Panel (ZRG2-GNM (03))
Project Start
1997-04-01
Project End
1999-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Cornell University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850