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: 8319313
• 负责人: Marija Drndic
• 金额: $ 43.87万
• 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/8319313
• 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.

描述（由申请人提供）：我们计划以我们最近发表的关于通过石墨烯纳米孔进行 DNA 易位的工作（Merchant 等人，Nano Lett. 10, 2915）以及我们在本申请中描述的其他初步结果为基础，开发一种 DNA 传感技术该技术基于测量单链 DNA 分子通过石墨烯纳米带 (GNR) 中的孔隙时的电流波动，预计这种几何形状会表现出大的电学特性。由于与每个核苷酸相关的独特静电势，每个核苷酸碱基的电流会发生变化，这些势能调节窄带中的电荷密度，从而改变相应的 GNR 电流水平，这与通过实验测量穿过 DNA 分子的隧道电流的方法形成鲜明对比。报道的电导差异约为 6 pS（Chang 等人，Nano Lett 10, 1070），建议的 GNR 是连续的，具有较大的面内电导差异。预计约为 1-10 mS（Nelson 等人，Nano Lett. 10, 3237）。石墨烯缺陷和散射效应可能会降低实际器件的电导率，但根据报告的 GNR 研究对这些预测进行了缩放。建议碱基间电导差为 1 ¿ S 是可以实现的。由于所需的信号非常大，因此可以容忍在更高的带宽下进行测量所产生的额外噪声，这消除了对定制高速的需要。高速超低噪声电子器件，因为许多现成的光纤光电二极管放大器都是针对这些电流和带宽范围而设计的，它还消除了在 DNA 分子易位时减慢或限制 DNA 分子的需要，因为测量。速度足够高，以防止分子的布朗波动使 GNR 信号模糊。我们提出的研究目标如下： 1. 制造适合 DNA 测序的原子薄、几纳米宽的 GNR 器件 2. 表征横向电学。原子薄 GNR 对四种核苷酸中的每一种的响应 3. 将这种传感机制发展为超快测序（>1 兆碱基/秒），并演示质粒 DNA 分子的测序。