DNA sequencing using single-layer graphene nanoribbons with nanopores

描述（由申请人提供）：我们计划建立在我们最近发表的关于通过石墨烯纳米孔的DNA易位的工作（Merchant等人，Nano Lett. 10，2915）和我们在本申请中描述的其他初步结果，以开发一种DNA传感技术，该技术基于测量当单链DNA分子易位通过石墨烯纳米带（GNR）中的孔时该石墨烯纳米带的电流波动。由于与每个核苷酸相关的独特静电势，预期这种几何结构对于每个核苷酸碱基表现出大的电流变化。这些电位调节窄带中的电荷密度，改变相应的GNR电流水平。 与测量通过DNA分子的隧穿电流的方法相反，其中实验报告的电导差异在6pS的量级（Chang等人，Nano Lett 10，1070），所提出的GNR是连续的，具有大的面内电导。基极-基极电导差预计为1-10 mS的量级（纳尔逊等人，Nano Lett. 10，3237）。石墨烯缺陷和散射效应可能会降低实际的器件电导，但基于GNR研究报告的这些预测表明，可以实现1 µ S的基极到基极电导差异。由于所需信号非常大，因此可以容忍在显著更高的带宽下进行测量所产生的额外噪声。我们预计，单碱基分辨率将在目前报道的DNA易位速度是可以实现的。 这消除了对定制高速超低噪声电子器件的需求，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，可以防止分子的布朗波动模糊GNR信号。 我们提出的研究目标如下： 1.制造适用于DNA测序的原子级薄、几nm宽的GNR器件2.表征原子薄GNRs对四种核苷酸中的每一种的横向电响应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。 公共卫生相关性：这项研究的目的是实现更快，更低成本的DNA测序，开发一种纳米尺寸的电子传感器，该传感器由原子级薄的碳片（称为石墨烯）构成。它将使我们能够确定潜在的遗传原因和症状，在患者中快速准确地检测这些疾病，并适当地治疗它们，从而在疾病的理解，诊断，治疗和预防方面取得重大进展。

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.