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. ? ? ?
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