DNA Sequencing Using Single Molecule Electronics

使用单分子电子学进行 DNA 测序

• 批准号: 9766330
• 负责人: Boyan Boyanov
• 金额: $ 46.81万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-16 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766330
• 关键词: Affect; Base Pairing; Biochemical; Carbon; Charge; Collaborations; Custom; DNA; DNA sequencing; DNA-Directed DNA Polymerase; Data; Development; Devices; Discrimination; Disease; Electronics; Enzyme Kinetics; Enzymes; Event; Foundations; Generations; Goals; Healthcare; Heart; Hybrids; Individual; Laboratory Research; Lead; Machine Learning; Massive Parallel Sequencing; Methods; Modality; Modernization; Modification; Monitor; Motion; Mutation; Nanotechnology; Noise; Nucleotides; Optics; Performance; Polymerase; Protein Engineering; Proteins; Publishing; Reading; Reproducibility; Research; Research Project Grants; Resolution; Route; Scientist; Signal Transduction; Single-Stranded DNA; Site; Surface; System; Techniques; Technology; Temperature; Transistors; Variant; Work; base; competitive environment; cost; enzyme activity; experimental study; improved; molecular modeling; nanoelectronics; nanopore; nanoscale; new technology; novel; response; scale up; single molecule; single walled carbon nanotube; solid state

PROJECT SUMMARY / ABSTRACT Progress in DNA sequencing has occurred through multiple stages of disruptive new technologies being introduced to the field, each of which has increased sequencing capabilities by lowering costs, improving throughput, and reducing errors. The goal of this research project is to investigate a new, all-electronic sequencing method that has the potential to become the next transformative step for DNA sequencing. This new method is based on single DNA polymerase molecules bound to nanoscale electronic transistors, a hybrid device that transduces the activity of a single polymerase molecule into an electronic signal. The goal of this research project is to determine whether these hybrid polymerase-transistors are truly applicable to DNA sequencing and the competitive environment of advanced sequencing technologies. To answer this question, the project teams the scientists who have developed the devices with Illumina, Inc., a worldwide leader in the DNA sequencing market. The experiments proposed here build on encouraging preliminary results, first to demonstrate accurate DNA sequencing and second to evaluate whether the new technique could become a competitive challenge to other sequencing methods. The interdisciplinary team will combine state-of-the-art techniques from protein engineering, nanoscale fabrication, and machine learning to customize polymerase's activity and its interactions with the electronic transistors. If successful, nanoscale solid-state devices like transistors provide one of the best opportunities for increasing sequencing capabilities while decreasing sequencing costs, so that DNA sequencing can become a standard technique in health care and disease treatment.

项目总结/摘要 DNA测序的进展是通过多个阶段的颠覆性新技术实现的 被引入该领域，其中每一种都通过降低成本，改善 吞吐量和减少错误。该研究项目的目标是研究一种新的全电子 这种测序方法有可能成为DNA测序的下一个变革性步骤。这 一种新的方法是基于单个DNA聚合酶分子与纳米级电子晶体管的结合， 将单个聚合酶分子的活性转换成电子信号的装置。 这项研究项目的目标是确定这些混合聚合酶-晶体管是否真的 适用于DNA测序和先进测序技术的竞争环境。到 为了回答这个问题，该项目与Illumina公司合作开发这些设备的科学家组成了团队，一 DNA测序市场的全球领导者。这里提出的实验建立在令人鼓舞的基础上 初步结果，首先是为了证明准确的DNA测序，其次是为了评估新的 技术可能成为对其他测序方法竞争性挑战。跨学科团队将 联合收割机结合了蛋白质工程、纳米制造和机器学习等最先进的技术， 定制聚合酶的活性及其与电子晶体管的相互作用。如果成功，纳米级 像晶体管这样的固态器件提供了提高排序能力的最佳机会之一 同时降低测序成本，使DNA测序成为医疗保健的标准技术， 和疾病治疗。

项目成果

Single-molecule Taq DNA polymerase dynamics.

• DOI: 10.1126/sciadv.abl3522
• 发表时间: 2022-03-11
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Turvey MW;Gabriel KN;Lee W;Taulbee JJ;Kim JK;Chen S;Lau CJ;Kattan RE;Pham JT;Majumdar S;Garcia D;Weiss GA;Collins PG
• 通讯作者: Collins PG