DNA sequencing using single-layer graphene nanoribbons with nanopores

使用具有纳米孔的单层石墨烯纳米带进行 DNA 测序

• 批准号: 8183217
• 负责人: Marija Drndic
• 金额: $ 61.52万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8183217
• 关键词: Address; Amplifiers; Base Sequence; Carbon; Charge; Chemicals; Custom; DNA; DNA Sequence; Defect; Deposition; Detection; Development; Devices; Diagnosis; Discrimination; Double-Blind Method; Electric Conductivity; Electromagnetics; Electronics; Electrostatics; Enzymes; Exhibits; Fiber Optics; Frequencies; Genetic; Genome; Goals; Individual; Length; Masks; Measurement; Measures; Methods; Motion; Noise; Nucleotides; Optics; Patients; Plasmids; Preparation; Process; Production; Property; Publishing; Reading; Reporting; Research; Resolution; Signal Transduction; Single-Stranded DNA; Speed; Structure; Symptoms; Techniques; Technology; Vision; Width; Work; base; cost; density; design; disorder prevention; irradiation; nano; nanopore; nanoscale; next generation; plasmid DNA; prevent; response; sensor; vapor; voltage

DESCRIPTION (provided by applicant): We plan to build on our recently published work on DNA translocation through graphene nanopores (Merchant et al., Nano Lett. 10, 2915) and other preliminary results we describe in this application, to develop a DNA sensing technology based on measuring the current fluctuations of a graphene nanoribbon (GNR) as a single-stranded DNA molecule translocates through a pore in that ribbon. This geometry is anticipated to exhibit large electrical current changes for each nucleotide base due to the unique electrostatic potential associated with each nucleotide. These potentials modulate the charge density in the narrow ribbon, altering the corresponding GNR current levels. In contrast to approaches which measure tunneling current through the DNA molecule, where experimentally reported conductance differences are on the order of 6 pS (Chang et al., Nano Lett 10, 1070), the proposed GNR is continuous, with a large in-plane conductance. Base-to-base conductance differences are predicted to be on the order of 1-10 mS (Nelson, et al., Nano Lett. 10, 3237). Graphene defects and scattering effects are likely to lower the practical device conductance, but scaling these predictions based on reported GNR studies suggest that base-to-base conductance differences of 1 ¿S could be achieved. The extra noise incurred by measuring at significantly higher bandwidth can be tolerated because the desired signals are so large. We anticipate that single-base resolution will be achievable at currently reported DNA translocation speeds. This eliminates the need for custom high-speed ultralow noise electronics, as many off-the-shelf photodiode amplifiers for fiber- optics are designed for these current and bandwidth ranges. It also removes the need to slow down or constrain the DNA molecule as it translocates, since the measurement speed is high enough to prevent Brownian fluctuations of the molecule from blurring the GNR signal. The aims of our proposed research are as follows: 1. Fabricate atomically-thin, few-nm wide GNR devices suitable for DNA sequencing 2. Characterize the transverse electrical response of atomically-thin GNRs to each of the four nucleotides 3. Develop this sensing mechanism into an ultrafast sequencing (>1 megabase/sec), and demonstrate the sequencing of plasmid DNA molecules. PUBLIC HEALTH RELEVANCE: This research aims to achieve much faster and lower-cost DNA sequencing with the development of a nanometer-sized electronic sensor constructed from an atomically-thin, carbon sheet known as graphene. It will enable major improvements in the understanding, diagnosis, treatment and prevention of disease, by allowing us to determine the underlying genetic causes and symptoms, detect these rapidly and accurately in patients, and treat them appropriately.

描述（应用程序提供）：我们计划基于我们最近发表的有关DNA易位的工作（Merchant等，Nano Lett。10，2915）和我们在本应用中描述的其他初步结果，以开发DNA感应技术，以测量通过单个sings dna dna pranffer transce transce transce transce transce transce transiper transi。由于与每种核前OTIDE相关的独特静电电势，预计几何形状会杀死每个核前底基碱基的大型电流变化。这些电势调节窄带中的电荷密度，从而改变了相应的GNR电流水平。与测量通过DNA分子进行隧穿电流的方法相反，在实验报告的电导差为6 ps的阶（Chang等，Nano Lett 10，1070）的阶，所提出的GNR是连续的，具有较大的平面电导率。碱到基电导差的差异预计为1-10毫秒（Nelson等，Nano Lett。10，3237）。石墨烯缺陷和散射效应可能会降低实际设备电导率，但是基于报告的GNR研究对这些预测进行缩放表明，可以实现1 s的碱基电导差异。由于所需的信号是如此之大，因此可以在显着较高的带宽下测得的额外噪声。我们预计，单基碱分辨率将在当前报道的DNA易位速度下成功。这消除了对自定义高速超速噪声电子设备的需求，因为许多用于光纤的现成光电二极管放大器都是为这些电流和带宽范围设计的。它还消除了在易位时减速或限制DNA分子的需求，因为测量速度足够高，可以防止分子的布朗波动使GNR信号模糊。我们提出的研究的目的如下：1。适合于DNA测序的原子上薄的，较少的NM宽的GNR设备2。表征对四个核苷酸的每个核苷酸3的横向电响应3。 公共卫生相关性：这项研究旨在通过开发由原子薄的碳薄片（称为石墨烯）构建的纳米尺寸的电子传感器来实现更快，更低的DNA测序。它将通过允许我们确定潜在的遗传原因和症状，快速，准确地检测到患者的理解，诊断，治疗和预防疾病的理解，诊断，治疗和预防疾病的重大改善，并适当治疗它们。