Nanoscale Fluidic Technologies for Rapidly Sequencing Single DNA Molecules

用于快速测序单个 DNA 分子的纳米级流体技术

• 批准号: 7688684
• 负责人: JOHN Michael RAMSEY
• 金额: $ 92.81万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7688684
• 关键词: Address; Arts; Attention; Base Pairing; Charge; Chemistry; DNA; Development; Devices; Dimensions; Discipline; Electrodes; Electron Transport; Electronics; Electrons; Experimental Designs; Future; Genetic; Genomics; Goals; Growth; Individual; International; Laboratories; Lateral; Lead; Length; Liquid substance; Measurement; Measures; Mechanics; Mediation; Metals; Molecular; Nanoscale Fluidic Technology; North Carolina; Nucleotides; Physics; Polymers; Polynucleotides; Positioning Attribute; Probability; Procedures; Research; Resolution; Science; Scientist; Semiconductors; Silicon; Structure; System; Technology; Tennessee; Time; Universities; Variant; Vertebral column; Work; base; commercially viable technology; interest; member; molecular dynamics; molecular scale; multidisciplinary; nanochannel; nanofabrication; nanofluidic; nanopore; nanoscale; nanowire; novel; particle beam; programs; prototype; quantum; research study; seal; simulation; single molecule; solid state; theories; tool; tool development

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.

描述（由申请人提供）：提出了一项研究计划，用于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。我们相信，基于第一原理计算，组成单链多核苷酸的各个核苷酸可以通过测量垂直于聚合物主链的各个单体单元的隧穿电流来区分。这种测量策略的执行需要开发至少两种技术能力;形成用于定位多核苷酸的纳米级流体通道，以及形成具有纳米级间距和横向范围的这些通道的相对电导探针。在这些实验的背景下，纳米尺度必须真正是分子尺度，在约1-2 nm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，用于制造设备，这将允许演示原理验证概念和进一步改进，以实现单碱基对分辨率。 我们的具体目标如下。 * 开发自上而下的制造程序，用于形成包含2 nm或更小的横向尺寸的流体纳米通道。 * 通过纳米通道的ss DNA易位的演示和表征。 * 开发横向尺寸小于2 nm的纳米电极的自下而上的制造策略。我们在（100）硅上发现的单向外延纳米线生长将被开发，以允许这些电极的制造。 * 实验表征电子输运概率分布函数，并与理论模拟进行比较。 * 确定区分不同类型核苷酸的实验可行性。分配误差与易位率将通过实验确定，并与模拟进行比较。 * 将演示通过横向电极电导测量的单基分辨率。