Nanoscale Fluidic Technologies for Rapidly Sequencing Single DNA Molecules

描述(由申请人提供)：提出了一项研究计划，以实现使用位于纳米级通道中的横向电导探针对DNA单分子进行测序的目标。我们认为，根据第一性原理计算，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干的单个单体单元的电隧穿电流来区分。这一测量战略的实施需要至少发展两种技术能力：形成用于定位多核苷酸的纳米级流体通道，以及与具有纳米级间距和横向范围的这些通道形成相反的电导探针。在这些实验的背景下，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纳米制造策略的组合，以制造能够证明原理概念并进一步改进以实现单碱基对分辨率的器件。 我们的具体目标如下所示。 *开发自上而下的制造程序，以形成横向尺寸为2纳米或更小的流体纳米通道。 *演示和表征通过纳米级通道的双链DNA移位。 *开发横向范围小于2纳米的自下而上的纳米电极制造策略。我们发现的在(100)硅上生长单边外延纳米线的发现将被开发出来，以允许制造这些电极。 *对电子传输概率分布函数进行了实验表征，并与理论模拟进行了比较。 *确定区分不同类型核苷酸的实验可行性。分配误差与移位率的关系将通过实验确定，并与模拟进行比较。 *将演示通过横向电极电导测量实现单基分辨率。

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.