NIRT: DNA Sequencing and Translocation Studies using Electrically-Addressable Nanopore Arrays

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This proposal was received in response to Nanoscale Science and Engineering initiative, NSF 03-043, category NIRT. The research program will utilize the complimentary expertise of the PI and co-PIs from different disciplines to develop a new generation of solid-state nanopore device that will allow measurements with unprecedented accuracies, and exploration of new DNA sequencing mechanisms. The NIRT team will: (1) Develop an electrically-addressable nanopore array (EANA) device and its related microfluid systems. (2) Develop a hybrid nanopore-in-nanopore system using EANA and biological nanopores, and carry out the first multiplexing Hemolysin nanopore experiments; (3) Explore the feasibility of sequence detection using SiO2 nanopores functionalized with polypeptide nucleic acid (PNA) molecules in the pore region; (4) Carry out an experimental test of a theoretical model proposed by a co-PI using single strand binding proteins to drive DNA translocation, and to examine its implications for sequencing; (5) Carry out a feasibility study of using the EANA technology for real-time monitoring of DNA degradation processes at single molecule level, and its potential for DNA sequencing. These NIRT activities will have broad impact in biological and biomedical research, in providing new techniques and more efficient analytical tools for studying biomolecules. The projects provide excellent training opportunities for postdoctoral and graduate students at the forefront of nanoscience and single-molecule biophysics and theoretical physics. The program also offers undergraduate students at Brown University and Harvard University new exciting research experience in the interdisciplinary field of nanobioscience. The students will receive advanced training in silicon nanofabrication, nano- and microfluidics, optics, molecular biophysics, and many-body statistical physics. These new skills will prepare the students for future careers in industry, academia, and public service. Funds for this award are provided by the Divisions of Physics and Materials Science in the Mathematical and Physical Sciences Directorate, the Division of Engineering Education and Centers in the Engineering Directorate, and the Division of Biological Infrastructure in the Directorate for Biological Sciences.