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DNA transport and sequencing through a quadrupole gate

通过四极门进行 DNA 运输和测序

基本信息

批准号：
7942683
负责人：
Charles R Vane
金额：
$ 27.87万
依托单位：
UT-BATTELLE, LLC-OAK RIDGE NATIONAL LAB
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7942683
关键词：
Calibration Carbon Carbon Nanotubes Characteristics Charge DNA DNA Sequence Detection Development Device Designs Devices Dimensions Electric Capacitance Electrodes Electromagnetics Electron Transport Electronics Electrons Electrostatics Environment Experimental Models Frequencies Genome Human Genome In Situ Ions Lead Measurement Measures Mechanics Medical Methods Modeling Molecular Nitrogen Noise Nucleotides Pathway interactions Pattern Positioning Attribute Quantum Theory Radio Reading Relaxation Resolution Scheme Signal Transduction Single-Stranded DNA Spectrum Analysis Speed Techniques Technology Testing Time Transistors Vision Work aqueous base clinical practice cost design electron beam lithography genome sequencing molecular dynamics molecular scale nanopore nanoscale novel prototype quantum simulation stem theories tool voltage

项目摘要

DESCRIPTION (provided by applicant): The purpose of this project is to develop a high speed device for sequencing a single strand DNA (ssDNA). The proposed device represents an alternative to nanopore sequencing with enhanced control capabilities both in translocation and detection. The central component of our device is a nanoscale quadrupole Paul trap that will be used for isolation, trapping, and localization of DNA and integrated with a detection circuitry for rapid sequencing of ssDNA. The proposed work builds on two important results from preliminary molecular dynamics and quantum-mechanical simulations. The first result confirms that a nanoscale quadrupole Paul trap is capable of effectively confining ions in an aqueous environment. The second result concerns the discovery of a quasi-resonant tunneling regime that results in several orders of magnitude increase in the transverse tunneling current using nitrogen doped carbon nanotube (CNT) electrodes. We envision designing a prototype nanoscale quadrupole Paul trap that can be used to explore various detection schemes based on the measurement of the transverse tunneling current and local capacitance. Specifically, to arrive at the best detection scheme to be integrated with the Paul trap in the final form of the sequencing device the feasibility of the following two novel detection schemes will be determined by modeling and experimental testing; (1) a radio-frequency single-electron transistor (RF SET), and (2) a nitrogen doped-CNT to measure the resonant tunneling current through the gap. To reduce device complexity the preliminary studies of the detection schemes will be performed separately from the Paul trap device. An advantage of a nanofabricated Paul trap is that a visible pathway for massively parallel sequencing device can be identified by using arrays of Paul traps. Device fabrication is further simplified by relaxation of critical dimension control that stems from the fact that the nm-size electrostatic trapping volume is much smaller than the fabricated dimensions (20-100nm). Direct sequencing using electronic measurements is potentially orders of magnitude faster than existing methods. The proportionally lower cost enables this technology to be used in everyday clinical practice for genome-based medical treatments. PROJECT HEALTH RELEVANCE An efficacious platform technology to sequence human genome by AC/DC electrical detection of DNA bases while DNA is translocated through a quadrupole nanogap. This will lead to a device that is capable for accurate genome sequencing many times cheaper and faster than currently available and will pave the way for in situ clinical practice of genome-based medical treatments.

描述（由申请人提供）：本项目的目的是开发一种用于单链DNA（ssDNA）测序的高速装置。所提出的装置代表了纳米孔测序的替代方案，其在易位和检测中具有增强的控制能力。我们的设备的核心组件是一个纳米级的四极保罗陷阱，将用于分离，捕获和定位的DNA和集成的检测电路的ssDNA的快速测序。拟议的工作建立在两个重要的初步分子动力学和量子力学模拟结果。第一个结果证实了纳米级四极Paul阱能够有效地将离子限制在水性环境中。第二个结果涉及发现的准共振隧穿制度，结果在几个数量级的横向隧穿电流增加使用氮掺杂的碳纳米管（CNT）电极。我们设想设计一个原型的纳米级四极保罗陷阱，可用于探索各种检测方案的基础上测量的横向隧穿电流和局部电容。具体地，为了达到与测序装置的最终形式中的Paul阱集成的最佳检测方案，将通过建模和实验测试来确定以下两种新颖检测方案的可行性：（1）射频单电子晶体管（RF SET），和（2）氮掺杂的CNT，以测量通过差距的共振隧穿电流。为了降低设备复杂性，检测方案的初步研究将与保罗陷阱设备分开进行。纳米制造的Paul阱的优点是可以通过使用Paul阱的阵列来鉴定用于大规模并行测序装置的可见途径。通过放宽临界尺寸控制来进一步简化器件制造，该临界尺寸控制源于nm尺寸的静电捕获体积远小于制造尺寸（20- 100 nm）的事实。使用电子测量的直接测序可能比现有方法快几个数量级。相对较低的成本使这项技术能够用于基于基因组的医学治疗的日常临床实践。一种有效的平台技术，通过AC/DC电检测DNA碱基，同时DNA通过四极纳米间隙移位，对人类基因组进行测序。这将导致能够进行精确基因组测序的设备比目前可用的便宜许多倍，速度更快，并将为基于基因组的医学治疗的原位临床实践铺平道路。