DNA transport and sequencing through a quadrupole gate

描述(申请人提供)：该项目的目的是开发一种用于单链DNA(单链DNA)测序的高速设备。拟议的设备代表了纳米孔测序的替代方案，在移位和检测方面都具有增强的控制能力。我们设备的中心组件是一个纳米级的四极Paul陷阱，它将用于DNA的分离、捕获和定位，并与用于单链DNA快速测序的检测电路集成在一起。拟议的工作建立在初步分子动力学和量子力学模拟的两个重要结果的基础上。第一个结果证实了纳米级四极保罗陷阱能够有效地限制水环境中的离子。第二个结果是发现了一种准共振隧穿机制，利用氮掺杂碳纳米管(CNT)电极可以使横向隧穿电流增加几个数量级。我们设想设计一个纳米级四极保罗势垒的原型，它可以用来探索基于横向隧道电流和局域电容测量的各种检测方案。具体地说，为了得到与测序设备的最终形式的Paul陷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型检测方案的可行性：(1)射频单电子晶体管(RF SET)，和(2)测量通过间隙的共振隧穿电流的氮掺杂碳纳米管。为了降低设备的复杂性，检测方案的初步研究将与Paul陷阱设备分开进行。纳米复合Paul陷阱的一个优点是，可以通过使用Paul陷阱阵列来识别大规模并行测序设备的可见路径。由于纳米尺寸的静电捕获体积比制造的尺寸(20-100 nm)小得多，因此放宽了临界尺寸控制，进一步简化了器件的制造。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疗的日常临床实践。项目健康相关性是一种有效的平台技术，通过交流/直流电检测DNA碱基，同时DNA通过四极纳米间隙移位来对人类基因组进行排序。这将导致一种能够进行精确基因组测序的设备，比目前可用的设备更便宜、更快，并将为基于基因组的医疗的现场临床实践铺平道路。

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.