DNA sequencing using single-layer graphene nanoribbons with nanopores

描述(由申请人提供)：我们计划在最近发表的关于通过石墨烯纳米孔进行DNA移位的工作的基础上再接再厉(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，该技术基于测量单链DNA分子通过石墨烯纳米带(GNR)中的孔时的电流波动。由于与每个核苷酸相关的唯一静电势，这种几何形状预计将显示每个核苷酸碱基的大电流变化。这些电势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分子的隧道电流的方法不同，其中实验报告的电导差约为6ps(Chang等人，Nano Lett 10,1070)，所提出的GNR是连续的，具有大的面内电导。碱基之间的电导差预计在1-10ms的数量级(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，但基于已报道的GNR研究的这些预测表明，基座到基座的电导差可能达到1？S。由于所需信号非常大，因此可以容忍在高得多的带宽下进行测量所产生的额外噪声。我们预计，以目前报道的DNA易位速度，单碱基的分辨率是可以实现的。这消除了定制高速超低噪声电子设备的需求，因为许多现成的光纤光电二极管放大器都是为这些电流和带宽范围而设计的。它还消除了在DNA分子移位时减缓或限制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模糊GNR信号。我们的研究目标如下：1.制作适合于DNA测序的原子薄、几纳米宽的GNR器件。2.表征原子薄GNR对四种核苷酸的横向电学响应。3.将这种传感机制发展成超快测序(&gt；1兆基数/秒)，并演示对质粒DNA分子的测序。 与公共健康相关：这项研究旨在通过开发一种纳米尺寸的电子传感器来实现更快、更低成本的DNA测序，该传感器由原子薄的碳片石墨烯组成。它将使我们能够确定潜在的遗传原因和症状，快速准确地在患者身上检测到这些原因和症状，并对他们进行适当的治疗，从而大大改进对疾病的理解、诊断、治疗和预防。

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.