Atomically-thin diode integrated into a nanopore DNA Sensor

集成到纳米孔 DNA 传感器中的原子薄二极管

• 批准号: 9808985
• 负责人: Rashid Bashir
• 金额: $ 21.62万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9808985
• 关键词: Address; Aluminum Oxide; Base Pairing; Biological; Characteristics; Chemicals; DNA; DNA Probes; DNA sequencing; Deposition; Detection; Development; Devices; Disease; Engineering; Genome; Goals; Hemolysin; Individuality; Length; Measurement; Measures; Mechanics; Membrane; Methods; Molecular Motors; Motion; Nucleotides; Principal Investigator; Reporting; Resolution; Signal Transduction; Sodium Chloride; Speed; System; Technology; Thinness; United States National Institutes of Health; base; cost; density; electric field; genome sequencing; graphene; high reward; high risk; human genome sequencing; improved; monolayer; nanometer; nanopore; nanoscale; new technology; next generation sequencing; novel; personalized medicine; prevent; programs; sensor; solid state; two-dimensional

Principal Investigator/Program Director (Last, First, Middle): Bashir, Rashid Summary: Sequencing the human genome has helped to improve our understanding of disease, inheritance and individuality. The growing need for cheaper and faster genome sequencing has prompted the development of new technologies that surpass conventional Sanger chain-termination methods in terms of speed and cost. These next-generation sequencing technologies — inspired by the $1,000 genome challenge proposed by the National Institutes of Health in 2004 — are beginning to revolutionize personalized medicine. Nanopore sensors are one of a number of DNA sequencing technologies that are currently poised to meet this challenge. Biological nanopores such as a-hemolysin and MspA, which consist of molecular motors anchored at the pore, have shown very promising results for ionic current based sequencing of ssDNA molecules, and systems using these pores are now being commercialized by Oxford Nanopores Technologies. However, biological nanopores do not provide the potential of direct single nucleotide read since the pore length spans 5-6 bases long. Solid-state nanopores using two-dimensional materials such as graphene, MoS2, and others could address this challenge regarding spatial resolution of sensing and controlling the DNA motion are addressed. As well as robustness and durability, the solid-state approach offers the ability to potentially fabricate high- density arrays of nanopores, attractive mechanical and chemical characteristics, and the possibility of integrating with novel electronic detection mechanisms. Despite the potential promise, to-date solid state nanopores have yet to demonstrate DNA sequencing, and resolving the challenges require discovering new mechanisms of sensing and translocation control. In this proposal, we introduce a completely new type of sensor which has the desired spatial resolution of sub nanometer and can potentially control the translocation of the DNA molecule. This high risk, high reward approach consists of engineering a nanometer scale out of plane diode using a 2D heterostructure consisting of crossed junction of monolayer MoS2 on monolayer WSe2. Unlike the nanopores in single monolayers, the new sensor allows multi-terminal measurements to probe different physical phenomena within the heterostructure simultaneously, enabling correlated measurements and control of the DNA translocation through the nanopore. The out of plane electric fields at the reverse bias junction will allow for sub nanometer spatial probing of the DNA molecule, and can also reduce the stringent requirement of measuring the change in in-plane conductivity of nanoribbons in which nanopores are formed. The applied biases and local electric field can also be used to control the translocation speed of the molecule. Understanding the relative contributions, interaction, and crosstalk of these different signals is the key scientific goal of this proposal. The key technological goal is to use the new readout schema to achieve single base pair resolution in sensing within a solid state nanopore.

首席研究员/项目总监（最后、第一、中间）：Bashir、Rashid 概括： 人类基因组测序有助于提高我们对疾病、遗传和疾病的理解 对更便宜、更快速的基因组测序的日益增长的需求促进了基因组测序的发展。 在速度和成本方面超越传统桑格链终止方法的新技术。 这些下一代测序技术——受到 1,000 美元基因组挑战的启发 美国国立卫生研究院 (National Institutes of Health) 于 2004 年开始革新个性化医疗。 传感器是目前准备应对这一挑战的众多 DNA 测序技术之一。 生物纳米孔，例如α-溶血素和MspA，由锚定在孔上的分子马达组成， 已经显示出基于离子电流的 ssDNA 分子测序以及使用的系统非常有希望的结果 这些孔现在已被牛津纳米孔技术公司商业化，然而，生物。 纳米孔不提供直接单核苷酸读取的潜力，因为孔长度跨越 5-6 个碱基 使用石墨烯、MoS2 等二维材料的固态纳米孔可以。 解决了有关传感和控制 DNA 运动的空间分辨率的这一挑战。 除了坚固性和耐用性之外，固态方法还提供了制造高性能的潜在能力。 纳米孔的密度阵列、有吸引力的机械和化学特性以及 尽管有潜在的希望，但迄今为止的固态。 纳米孔尚未证明 DNA 测序，解决这些挑战需要发现新的 传感和易位控制机制。 在本提案中，我们引入了一种全新类型的传感器，其具有亚级所需的空间分辨率 纳米技术可以潜在地控制DNA分子的易位，这种高风险、高回报。 该方法包括使用二维异质结构设计纳米级平面外二极管，该二维异质结构包括 单层MoS2在单层WSe2上的交叉结与单个单层中的纳米孔不同。 新的传感器允许多终端测量来探测不同的物理现象 同时异质结构，实现 DNA 易位的相关测量和控制 通过纳米孔，反向偏置结场处的平面外电场将允许亚纳米级。 DNA分子的空间探测，还可以降低测量变化的严格要求 形成纳米孔的纳米带的面内电导率。 场还可用于控制分子的相对易位速度。 这些不同信号的贡献、相互作用和串扰是该提案的关键科学目标。 关键技术目标是使用新的读出模式来实现传感中的单碱基对分辨率 在固态纳米孔内。