DNA Sequencing with novel 2D FET-nanopore devices

使用新型 2D FET 纳米孔器件进行 DNA 测序

基本信息

批准号：
9920755
负责人：
Marija Drndic
金额：
$ 31.16万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2022-04-30
项目状态：
已结题

项目摘要

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.

项目概要我们建议通过以下方式证明单 DNA 碱基歧视的原理验证利用新兴二维的单原子厚度和电学特性材料（与核苷酸之间的间隔一样薄） DNA 的直接读数。通过测量流过电流的调制序列可能是可能的单层新型 2D 纳米带 (NR) FET，超越石墨烯，由每个单链 DNA 分子通过纳米孔 (NP) 时的碱基 NR。预计这种几何形状会表现出较大的电流变化。核苷酸碱基由于与每个相关的独特静电势这些电位调节窄 2D FET NR 中的电荷密度，这种方法的主要好处是改变相应的 NR 电流水平。 NR 可以产生大电流，从而有可能实现高速测量。与基于离子电流的测序相比，这种方法更新且风险较高，并且这是非常令人兴奋的，因为预测信号水平 ~ µA 或更高，该方法特别解决了这三个问题。基于纳米孔的测序的主要障碍：1）我们的方法规避了这一需求减慢 DNA 通过孔的运动，2) 预测的电子差异每个碱基的电流足够大，我们预计信噪比将即使在本机速度下，也足够大以进行碱基歧视，并且 3）序列读出方法与多重检测兼容。我们集团已经进行了可行性测试，但该项目仍在进行中探索性的，适合R21社区之前的努力，涉及。开创性的碳纳米管 NP FET（例如 Golovchenko 的实验室）以及最近，尽管有这些结果，但 Drndic、Radenovic 和 Dekker 实验室的石墨烯-NP FET。即使在亚 10 nm 宽度时，也能测量石墨烯 NR-NP FET 的性能，可能是由于缺乏显着的带隙和石墨烯的疏水性，这里我们专注于一种更有前途、更新的单原子薄材料作为候选材料这些 NR 通道具有可调带隙，并且更加亲水，包括：二维金属二硫属化物（MoS2、WS2）和磷烯。我们之前测试过 20 – 200 nm 宽的单带有 NP 的层状石墨烯 NR 最多可承载 10 1 mM 至 1M KCl 溶液中的 µA，带宽为我们还开发了一种高达 100 MHz 的方法。在不降低 2D NR 的情况下钻 NP 电导和观察到的相关 NR 和双链 DNA 易位过程中的离子信号。预计单碱基分辨率可能是根据目前报道的 DNA 可实现易位速度（106 个碱基/秒）。无需定制高速超低噪声电子器件，与许多现成的一样用于光纤的光电二极管放大器是专为这些电流和带宽而设计范围。插图：2016 年 ACS Nano 封面艺术说明磷烯（磷的二维片原子）纳米带（和纳米孔）开发于 Drndic 实验室，除了 2D 之外，还将在这项工作中进行测试金属二硫族化物 NR FET。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Stochastic Ionic Transport in Single Atomic Zero-Dimensional Pores.

单原子零维孔中的随机离子传输。

DOI：
发表时间：
2020-09-22
期刊：
影响因子：
17.1
作者：
Thiruraman, Jothi Priyanka;Masih Das, Paul;Drndić, Marija
通讯作者：
Drndić, Marija

In Situ 2D MoS2 Field-Effect Transistors with an Electron Beam Gate.

具有电子束门的原位 2D MoS2 场效应晶体管。

DOI：
发表时间：
2020-06-23
期刊：
影响因子：
17.1
作者：
Masih Das, Paul;Drndić, Marija
通讯作者：
Drndić, Marija

Mixed-Dimensional 1D/2D van der Waals Heterojunction Diodes and Transistors in the Atomic Limit.

原子极限下的混合维一维/二维范德华异质结二极管和晶体管。

DOI：
发表时间：
2022-01-25
期刊：
影响因子：
17.1
作者：
Jadwiszczak, Jakub;Sherman, Jeffrey;Lynall, David;Liu, Yang;Penkov, Boyan;Young, Erik;Keneipp, Rachael;Drndić, Marija;Hone, James C;Shepard, Kenneth L
通讯作者：
Shepard, Kenneth L

Ions and Water Dancing through Atom-Scale Holes: A Perspective toward "Size Zero".

离子和水在原子级孔中跳舞：“零尺寸”的视角。