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

项目摘要 我们建议开发一种基于纳米孔的传感的新范例，包括离子喷泉纳米孔读取器 (IFNRS)。在这些设备中，DNA或RNA分子通过一个亚2纳米的小孔移动，并通过电子传感 通过记录离子在主体和主体之间来回流动的速率来获得DNA序列的 膜内含有孔洞的非常小的空间。该设备的一个关键部件是 与MXenes有关的二维层状材料，具有导电、亲水和大多数 重要的是，在它们的片层之间的间隙区域插入各种阳离子。我们最近做了 开发了一种单层和双层MXene薄片的晶片规模组装方法 自发地组织成大面积导电有序薄膜的马赛克。通过制造双层 MXene薄膜，直径小于2 nm的孔穿过它，我们创造了一个离子喷泉，可以存储和释放离子 通过让它们通过毛孔开口。这种纳米孔传感器的主要优点是 在孔的一侧消除了访问阻力，这超过了基本分辨率限制 传统的纳米孔传感技术。这种类型的设备的另一个优点是物理上较厚的毛孔可以 在制备的同时仍显示出原子薄纳米孔膜的分辨率。我们正在提议 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，以及用于基本计算的软件。如果成功，我们的设备将能够阅读 DNA/RNA比最先进的技术更快(1,000个碱基每秒)，而且更高的检测速度 精确度各种类型的DNA和RNA碱基修饰。

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.