Nanoscale Fluidic Technologies for Rapidly Sequencing Single DNA Molecules

描述（由申请人提供）：提出一项研究计划，旨在利用位于纳米级通道中的横向电导探针实现DNA单分子测序的目标。我们相信，基于第一性原理计算，组成单链多核苷酸的单个核苷酸可以通过测量垂直于聚合物主链的单个单体单元的隧穿电流来区分。执行这一度量策略需要开发至少两种技术能力；多核苷酸定位的纳米级流体通道的形成，以及这些通道具有纳米级间距和横向范围的反向电导探针的形成。在这些实验中，纳米尺度必须是真正的分子尺度，在大约1-2纳米的范围内。将探索自下而上和自上而下的纳米制造策略的组合，以制造设备，这些设备将允许原理验证概念的演示和进一步改进，以实现单碱基对分辨率。

DESCRIPTION (provided by applicant): 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.