Ion Fountain Nanopore Readers for High-Resolution DNA and RNA Sequencing

用于高分辨率 DNA 和 RNA 测序的 Ion Fountain 纳米孔读数器

• 批准号: 10204556
• 负责人: Meni Wanunu
• 金额: $ 32.8万
• 依托单位: NORTHEASTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10204556
• 关键词: Architecture; Area; Back; Biological Sciences; Caliber; Cations; Chemicals; Complex; Computer software; DNA; DNA Modification Process; DNA Sequence; DNA biosynthesis; DNA sequencing; Detection; Development; Devices; Disease; Electrolytes; Electronics; Epigenetic Process; Exhibits; Film; Genetic Diseases; Genomic DNA; Genomic Segment; Genomics; Gold; Immobilization; Ions; Kinetics; Longevity; Malignant Neoplasms; Measurement; Measures; Mediating; Membrane; Methods; Modification; Monitor; Mosaicism; Network-based; Nucleic acid sequencing; Nucleotides; Oligonucleotides; Optics; Organism; Phase; Physiologic pulse; Play; Production; RNA; RNA Sequences; Reader; Resistance; Resolution; Role; Side; Signal Transduction; Silanes; Single-Stranded DNA; Sodium Chloride; Structure; System; Technology; Thick; Thinness; Time; Training; Variant; base; cost; design; detection sensitivity; ds-DNA; electrical property; experimental study; helicase; hydrophilicity; improved; intercalation; interstitial; link protein; monolayer; nanopore; neural network; phosphonate; real time monitoring; reference genome; sensor; silicon nitride; single molecule; single molecule real time sequencing; solid state; transcriptome sequencing; two-dimensional; voltage

Project Summary We propose to develop a new paradigm in nanopore-based sensing, involving ion-fountain nanopore readers (IFNRs). In these devices, a DNA or RNA molecule is moved through a sub-2-nm pore, and electronic sensing of the DNA sequence is made by recording the rate at which ions floss back and forth between the bulk and the very small volume of space within the membrane that contains the pore. A key component of the device is related to MXenes, two-dimensional layered materials that are electrically conductive, hydrophilic, and most importantly, intercalate various cations in the interstitial region between their sheets. We have recently developed a method for waferscale assembly of monolayer and bilayer MXene sheets in which MXene flakes spontaneously organize to a mosaic of electrically conductive large-area ordered films. By making a bilayer MXene film with a sub-2-nm diameter hole through it, we create an ion fountain that stores and releases ions by passing them through the pore opening. The main advantage of this type of a nanopore sensor is that access resistance is eliminated on one side of the pore, which beats fundamental resolution limits of conventional nanopore sensing. Another advantage of this type of a device is that a physically thicker pore can be fabricated while still exhibiting a resolution of an atomically-thin nanopore membrane. We are proposing here to develop the IFNR architecture, supplemental electronics measurement platform that allows DNA and RNA capture and readout, and software for basecalling. If successful, our devices will be able to read DNA/RNA faster than state-of-the-art technology (>1,000 bases per second) and further, detect at high accuracy various types of DNA and RNA base modifications.

项目摘要 我们建议开发一种新的范例，在纳米孔为基础的传感，涉及离子喷泉纳米孔读者 （IFNRs）。在这些设备中，DNA或RNA分子通过一个亚2纳米的孔移动， 通过记录离子在主体和主体之间来回摆动的速率， 膜内包含孔的非常小的空间体积。该装置的一个关键部件是 与MXene相关，MXene是导电的、亲水的、且大多数 重要的是，在它们的片层之间的间隙区域中插入各种阳离子。我们最近 开发了一种用于单层和双层MXene片材的晶圆级组装的方法，其中MXene薄片 自发组织成导电大面积有序膜的镶嵌体。通过制造一个双层 MXene薄膜上有一个直径小于2纳米的孔，我们创造了一个离子喷泉，可以储存和释放离子 通过使它们穿过孔开口。这种类型的纳米孔传感器的主要优点是， 在孔的一侧消除了进入阻力，这超过了 传统的纳米孔传感。这种类型的装置的另一个优点是物理上较厚的孔可以 同时仍然表现出原子级薄的纳米孔膜的分辨率。我们提议 在这里开发IFNR架构，补充电子测量平台，允许DNA和 RNA捕获和读出，以及碱基判定软件。如果成功，我们的设备将能够读取 DNA/RNA比最先进的技术更快（每秒> 1，000个碱基），而且， 各种类型的DNA和RNA碱基修饰的准确性。