DNA Sequencing with novel 2D FET-nanopore devices

项目摘要 我们建议通过以下方式证明原则证明单DNA碱基歧视 利用新出现的2D的单原子厚度和电学性质 物质(就像核苷酸之间的分离一样薄)。直接读出DNA 序列可以通过测量流经 石墨烯以外的单层新型2D纳米带(NR)FET 当单链DNA分子通过纳米孔(NP)时，它的碱基 天然橡胶。这一几何形状预计将显示出较大的电流变化 核苷酸碱基，因为每个碱基都具有独特的静电势 核苷酸。这些电势调制窄2D FET NR中的电荷密度， 改变相应的NR当前水平。这种方法的主要好处是 CAN NR可能会产生大电流，从而可能实现高速测量。 与基于离子电流的测序相比，这种方法更新，风险也更高，而且 这非常令人兴奋，因为信号电平~µA或更高被预测为 多路复用高带宽测序。这种方法特别解决了三个问题 纳米孔测序的主要障碍：1)我们的方法避开了 以减缓DNA在毛孔中的运动，2)预测的电子差异 每个基座的电流都足够大，我们预计信噪比将 即使在这种本机速度下，也要大到足以区分基数，以及3) 序列读出方法兼容多路检测。重要 我们集团已经进行了可行性试验，但这个项目还在进行中 探索性的，适合R21。社区中以前的努力，涉及 开创性的碳纳米管-NP FET(例如，Golovchenko的实验室)和最近， Drndic、Raddovic和Dekker实验室的石墨烯-NP FET。尽管有这些结果，但由于 对测量的石墨烯NR-NP FET的性能即使在亚10 nm宽度时， 可能是由于缺乏明显的带隙，以及石墨烯的疏水性，在这里 我们专注于一种更有前途的、更新的单原子薄膜材料作为候选者 2D通道。这些NR具有可调的带隙，并且更亲水，包括： 二维二卤化物(MoS_2，WS_2)和膦。 我们之前测试了20-200 nm宽的单 携带多达10个纳米粒子的石墨烯负载层 1 mm至1M KCl溶液中的微安，带宽为 高达100兆赫。我们还开发了一种方法来 在不降低2D NR的情况下钻NPs 电导和观测到的相关NR和 DsDNA易位过程中的离子信号。我们 预计单基分辨率可能是 在目前报告的DNA中可以实现 易位速度(106垒/S)。这 不再需要定制的高速 超低噪音电子产品，就像许多现成的 用于光纤的光电二极管放大器 为这些电流和带宽而设计 范围。 插图：2016年的ACS Nano封面艺术 图解磷烯(一张二维磷片 原子)纳米带(和纳米孔)在 博士实验室，除2D外，还将在本工作中进行测试 金属二卤化物NR场效应管。

Project Summary We propose to demonstrate proof-of-principle single DNA base discrimination by harnessing the one-atom thickness and electrical properties of newly emerging 2D materials (as thin as the separation between nucleotides). A direct readout of the DNA sequence may be possible by measuring the modulation of the current flowing through a single-layer novel 2D nanoribbon (NR) FET, beyond graphene, induced by each base in a single-stranded DNA molecule as it passes through a nanopore (NP) in that NR. 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 2D FET NR, altering the corresponding NR current levels. The major benefit of this approach is that can NR may produce large currents, potentially enabling measurements at high speed. This approach is newer and high-risk, compared to ionic-current-based sequencing, and it is tremendously exciting because signal levels ~ µA or higher are predicted, towards multiplexed high-bandwidth sequencing. This approach particularly addresses the three key obstacles to nanopore-based sequencing: 1) our approach circumvents the need to slow down DNA motion through the pore, 2) the predicted differences in electronic current for each base are large enough that we anticipate the signal-to-noise ratio will be large enough for base discrimination, even at this native speed, and 3) the sequence readout method is compatible with multiplexed detection. Important feasibility tests have already been realized in our group, but this project is still exploratory and suitable for the R21. Previous efforts in the community, involved pioneering carbon nanotube-NP FETs (e.g.,Golovchenko’s lab) and more recently, graphene-NP FETs by Drndic, Radenovic, and Dekker labs. Despite these results, due to the performance of measured graphene NR-NP FETs even when sub-10-nm-width, probably due to lack of significant bandgap, and the hydrophobicity of graphene, here we focus on a more promising, newer class of single-atom thin materials as candidate 2D channels. These NRs have tunable bandgaps and are more hydrophilic and include: 2D metal dichalcogenides (MoS2, WS2) and phosphorene. We previously tested 20 – 200 nm wide single- layer graphene NRs with NPs carrying up to 10 µA in 1 mM to 1M KCl solution at bandwidths as high as 100 MHz. We also developed a way to drill NPs without lowering the 2D NR conductance and observed correlated NR and ionic signals during dsDNA translocation. We anticipate that single-base resolution may be achievable at currently reported DNA translocation speeds (106 bases/s). 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. Illustration: The ACS Nano Cover Art from 2016 illustrating phosphorene (a 2D sheet of phosphorous atoms) nanoribbons (and nanopores) developed in Drndic lab, to be tested in this work, in addition to 2D metal dichalcogenides NR FETs.