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.

项目摘要我们建议通过利用新出现的2D的一个原子厚度和电气特性材料（与核苷酸之间的分离一样薄）。 DNA的直接读数通过测量流过A的电流的调制，可能是可能的单层小说2D纳米替比（NR）FET，超出石墨烯，每种诱导基于单链的DNA分子，因为它通过纳米孔（NP） nr。预计这种几何形状会杀死每种几何电流变化核苷酸基底部由于与每种相关的独特静电电势核苷酸。这些电势调节狭窄2D FET NR中的电荷密度，改变相应的NR电流水平。这种方法的主要好处是 NR可以产生大型电流，有可能在高速下启用测量。与基于离子电流的测序相比，这种方法是新的和高风险的，并且这是非常令人兴奋的，因为预测信号水平〜μa或更高多路复用的高带宽测序。这种方法特别解决了这三个基于纳米孔的测序的关键障碍：1）我们的方法规避了需求要减慢DNA通过孔的运动，2）电子的预测差异每个基数的电流足够大，我们预计信噪比将会即使以这种本地速度，也足够大以进行基础歧视，3）序列读取方法与多路复用检测兼容。重要的我们的小组已经实现了可行性测试，但是这个项目仍在探索性，适合R21。社区的以前努力，参与开创性的碳纳米管NP Fets（例如Golovchenko的实验室），最近 Drndic，Radenovic和Dekker Labs的石墨烯-NP FET。尽管有这些结果，到期即使在低于10 nm的宽度时，测得的石墨烯NR-NP FET的性能，可能是由于缺乏明显的带隙和石墨烯的疏水性我们专注于更新的，更新的单原子薄材料作为候选人 2D通道。这些NR具有可调的带镜头，并且更亲密，包括： 2D金属二甲植物（MOS2，WS2）和磷烯。我们以前测试了20 - 200 nm宽的单个层石墨烯NR，NP最多可携带10 在带宽处的1 mm至1M KCl溶液中µA 高达100 MHz。我们还开发了一种方法钻NP而不降低2D NR 电导和观察到的相关NR和 DsDNA易位期间的离子信号。我们预计单基准分辨率可能是当前报道的DNA可以实现易位速度（106个基础/s）。这消除了自定义高速的需求超级噪声电子，许多现成的光纤启动的光电二极管放大器是专为这些当前和带宽而设计范围。插图：2016年的ACS Nano封面艺术说明磷烯（2D磷原子）在除2D外，还需要在这项工作中测试Drndic Lab 金属二分法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）

Engineering adjustable two-pore devices for parallel ion transport and DNA translocations

工程可调双孔装置用于平行离子传输和 DNA 易位

DOI：
10.1063/5.0044227
发表时间：
2021
期刊：
The Journal of Chemical Physics
影响因子：
0
作者：
Chou, Yung-Chien;Chen, Joshua;Lin, Chih-Yuan;Drndić, Marija
通讯作者：
Drndić, Marija

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

DOI：
10.1021/acsnano.1c10524
发表时间：
2022-01-25
期刊：
ACS NANO
影响因子：
17.1
作者：
Jadwiszczak, Jakub;Sherman, Jeffrey;Lynall, David;Liu, Yang;Penkov, Boyan;Young, Erik;Keneipp, Rachael;Drndic, Marija;Hone, James C.;Shepard, Kenneth L.
通讯作者：
Shepard, Kenneth L.

Computer vision AC-STEM automated image analysis for 2D nanopore applications

适用于 2D 纳米孔应用的计算机视觉 AC-STEM 自动图像分析

DOI：
10.1016/j.ultramic.2021.113249
发表时间：
2021
期刊：
Ultramicroscopy
影响因子：
2.2
作者：
Chen, Joshua;Balan, Adrian;Masih Das, Paul;Thiruraman, Jothi Priyanka;Drndić, Marija
通讯作者：
Drndić, Marija

Large area few-layer TMD film growths and their applications