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 我们建议在基于纳米孔的传感中开发一个新的范式，涉及离子纳米孔的读取器 （IFNRS）。在这些设备中，DNA或RNA分子通过亚2-nm孔移动，电子传感 DNA序列的数量是通过记录散装和在散装之间来回牙线的速率来制作的 包含孔的膜内的空间很小。设备的关键组件是 与MXENES，二维分层材料有关，这些材料具有导电性，亲水性和大多数 重要的是，在其床单之间的间隙区域中的各种阳离子进行了插入。我们最近有 开发了一种用于单层和双层mxene片的瓦金楼组装的方法，其中mxene薄片 自发地组织到导电大区域有序膜的镶嵌物中。通过制作双层 MXENE膜通过它的直径为2-nm的孔，我们创建了一个离子喷泉，存储和释放离子 通过将它们穿过孔口开口。这种类型的纳米孔传感器的主要优点是 孔的一侧消除了访问电阻，这超过了基本的分辨率限制 常规的纳米孔感应。这种设备的另一个优点是，物理上更厚的孔可以 在仍表现出原子上薄的纳米孔膜的分辨率时被制造。我们正在提议 在这里开发IFNR体系结构，补充电子测量平台，该平台允许DNA和 RNA捕获和读数以及用于基本的软件。如果成功，我们的设备将能够阅读 DNA/RNA比最先进的技术快（每秒> 1,000个基础），然后在高处检测到 精度各种类型的DNA和RNA碱基修饰。