DNA Sequencing with novel 2D FET-nanopore devices

使用新型 2D FET 纳米孔器件进行 DNA 测序

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/9920755
• 关键词: Address; Amplifiers; Arts; Caliber; Carbon Nanotubes; Charge; Communities; Custom; DNA; DNA Sequence; DNA sequencing; Development; Devices; Diagnosis; Disadvantaged; Discrimination; Electronics; Electrostatics; Enzymes; Exhibits; Fiber Optics; Genetic; Geometry; Goals; Hydrophobicity; Length; Measurement; Measures; Metals; Methods; Motion; Noise; Nucleotides; Patients; Performance; Phosphorus; Positioning Attribute; Reading; Reporting; Research; Resolution; Side; Signal Transduction; Single-Stranded DNA; Sodium Chloride; Speed; Symptoms; Techniques; Technology; Testing; Thick; Thinness; Transistors; Transition Elements; Variant; Width; Work; base; cost; density; design; disorder prevention; ds-DNA; electrical property; experimental study; graphene; high risk; hydrophilicity; multiplex detection; nano; nanopore; nanoscale; next generation; novel; operation; sensor; voltage

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.

项目总结

项目成果

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
• 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.

Large area few-layer TMD film growths and their applications

• DOI: 10.1088/2515-7639/ab82b3
• 发表时间: 2020-04-01
• 期刊: JOURNAL OF PHYSICS-MATERIALS
• 影响因子: 4.8
• 作者: Mandyam, Srinivas V.;Kim, Hyong M.;Drndic, Marija
• 通讯作者: Drndic, Marija

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