A research program is proposed for achieving the goal of sequencing single molecules of DNA using transverse conductance probes located in a nanoscale channel. We believe, based upon first principle calculations, that the individual nucleotides making up a single strand polynucleotide can be distinguished by measuring the electrical tunneling current through the individual monomeric units perpendicular to the polymer backbone. The execution of this measurement strategy requires the development of at least two technological capabilities;the formation of nanometer scale fluidic channels for the localization of the polynucleotide and the formation of opposed conductance probes with these channels with nanoscale spacing and lateral extent. Nanoscale in the context of these experiments must truly be of molecular scale, in the range of about 1-2 nm. A combination of bottom-up and top-down nanofabrication strategies will be explored for the fabrication of devices that will allow demonstration of proof-of-principle concepts and further refinement to achieve single base-pair resolution.
Our specific aims are listed below. * Develop top-down fabrication procedures for formation of fluidic nanochannels containing lateral dimensions of 2 nm or less. * Demonstration and characterization of ss DNA translocation through nanoscale channels. * Develop bottom-up fabrication strategies of nanoelectrodes with a lateral extent of less than 2 nm. Our discovery of unilateral epitaxial nanowire growth on (100) silicon will be developed to allow fabrication of these electrodes. * Experimentally characterize electron transport probability distribution functions and compare to theoretical simulations. * Determine experimental feasibility of distinguishing different types of nucleotides. Assignment error versus translocation rates will be experimentally determined and compared to simulations. * Single-base resolution by transverse electrode conductance measurements will be demonstrated.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG002647-06
Application #
7688684
Study Section
Special Emphasis Panel (ZHG1-HGR-N (O1))
Program Officer
Schloss, Jeffery
Project Start
2004-09-30
Project End
2013-08-31
Budget Start
2009-09-01
Budget End
2013-08-31
Support Year
6
Fiscal Year
2009
Total Cost
$928,135
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Pedersen, Jonas Nyvold; Boynton, Paul; Ventra, Massimiliano Di et al. (2017) Classification of DNA nucleotides with transverse tunneling currents. Nanotechnology 28:015502
Menard, Laurent D; Ramsey, J Michael (2013) Electrokinetically-driven transport of DNA through focused ion beam milled nanofluidic channels. Anal Chem 85:1146-53
Iancu, Violeta; Zhang, X-G; Kim, Tae-Hwan et al. (2013) Polaronic transport and current blockades in epitaxial silicide nanowires and nanowire arrays. Nano Lett 13:3684-9
Krems, Matt; Di Ventra, Massimiliano (2013) Ionic Coulomb blockade in nanopores. J Phys Condens Matter 25:065101
Wilson, James; Di Ventra, M (2013) Single-base DNA discrimination via transverse ionic transport. Nanotechnology 24:415101
Iancu, V; Kent, P R C; Hus, S et al. (2013) Structure and growth of quasi-one-dimensional YSi2 nanophases on Si(100). J Phys Condens Matter 25:014011
Menard, Laurent D; Mair, Chad E; Woodson, Michael E et al. (2012) A device for performing lateral conductance measurements on individual double-stranded DNA molecules. ACS Nano 6:9087-94
Menard, Laurent D; Ramsey, J Michael (2011) Fabrication of sub-5 nm nanochannels in insulating substrates using focused ion beam milling. Nano Lett 11:512-7
Cui, Shengting (2011) Dynamics of ion migration in nanopores and the effect of DNA-ion interaction. J Phys Chem B 115:10699-706
Zwolak, Michael; Wilson, James; Di Ventra, Massimiliano (2010) Dehydration and ionic conductance quantization in nanopores. J Phys Condens Matter 22:454126

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