DNA sequencing using single-layer graphene nanoribbons with nanopores

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）和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孔易位时石墨烯纳米带（GNR）的电流波动。由于与每个核苷酸相关的独特静电电位，这种几何形状预计会表现出每个核苷酸碱基的大电流变化。这些电位调节窄带中的电荷密度，改变相应的GNR电流水平。与通过DNA分子测量隧道电流的方法相比，实验报告的电导差异约为6 pS (Chang等人，Nano Lett 10,1070)，所提出的GNR是连续的，具有较大的面内电导。碱基之间的电导差异预计在1-10毫秒量级（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，但根据已报道的GNR研究缩放这些预测表明，可以实现1¿S的基间电导差异。由于所需的信号非常大，因此可以容忍在明显更高的带宽下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易位速度下实现。这消除了定制高速超低噪声电子器件的需要，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。由于测量速度足够高，可以防止分子的布朗波动使GNR信号变得模糊，因此它也不需要在DNA分子易位时减慢或限制DNA分子。我们提出的研究目的如下：1。制造适合DNA测序的原子级薄、几纳米宽的GNR器件。表征原子薄的gnr对四种核苷酸的横向电响应3。将该传感机制发展为超快测序（100兆/秒），并演示质粒DNA分子的测序。

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.