Integrated Nanochannel and Nanopore Architecture for Studying Translocation Dynamics of DNA

脱氧核糖核酸（DNA）链上的碱基序列决定了一个人的遗传特征和他或她对疾病的易感性。该序列可用于定制常规治疗方法，并根据个体的遗传组成提供更个性化的药物。固态纳米孔和纳米通道为DNA测序提供了新的范例，并且可以使序列测定比目前使用的方法更快，更便宜。然而，这些纳米级工具还不能实现大规模商业应用所需的必要控制和再现性。该奖项支持开发集成纳米级架构的基础研究，该架构可以利用固态纳米孔和纳米通道的优点进行受控DNA分析。新平台将加速DNA测序研究，并有可能使个性化医疗成为临床现实。这项研究还将为教学、培训和学习提供丰富的基础，并为纳米级制造和计量打开一扇新的窗口。该计划还将有广泛的推广组成部分，包括积极招募和培训妇女和工程中代表性不足的少数民族，纳米孔传感器有望通过消除对化学转化和合成的需要以及使用长读取长度来彻底改变DNA测序技术。然而，快速的DNA移位速度和低信噪比提出了需要克服的科学障碍，以实现这些传感器的全部应用潜力。这项研究的目的是展示必要的技术，设计，制造和组装集成的纳米级架构，通过纳米孔研究DNA易位，以及了解基本的科学原理，管理易位的长DNA分子（100 kb）使用同时的电和光信号读出。这项研究的结果将带来一个新的生物分析平台，可用于捕获具有高时间分辨率的综合遗传数据。在这项研究中，将设计和制造一个集成的纳米通道-纳米孔装置，其中纳米通道将用于解开长螺旋DNA并将拉伸的分子送入纳米孔，这反过来又将用于识别DNA的结构特征。对长DNA链的纳米孔易位的基本物理学的理解和控制这种易位动力学的能力将有助于实现基于纳米孔的DNA测序仪。

The sequence of bases on deoxyribonucleic acid (DNA) strand determines an individual's hereditary traits and his or her susceptibility to diseases. This sequence can be used to tailor conventional therapeutic approaches and deliver more personalized medicine based on an individual's genetic makeup. Solid-state nanopores and nanochannels present a new paradigm for DNA sequencing and can make sequence determination faster and cheaper than the currently used methods. However, these nanoscale tools have not been able to achieve the necessary control and reproducibility required for large-scale commercial applications. This award supports fundamental research for the development of an integrated nanoscale architecture that can harness the merits of both the solid-state nanopores and the nanochannels for controlled DNA analysis. The new platform will accelerate DNA sequencing research and has the potential to make personalized medicine a clinical reality. This research will also provide a rich foundation for teaching, training, and learning and open a new window to manufacturing and metrology at nanoscale. The program will also have extensive outreach component, including active recruitment and training of women and underrepresented minorities in engineering,Nanopore sensors are poised to revolutionize DNA sequencing technology by obviating the need for chemical conversion and synthesis and by use of long read lengths. However, fast DNA translocation speed and low signal-to-noise ratio present scientific barriers that need to be overcome to realize the full application potential of these sensors. The objective of this research is to demonstrate enabling technologies necessary to design, fabricate, and assemble integrated nanoscale architecture for studying DNA translocation through nanopores, as well as to understand fundamental scientific principles that govern the translocation of long DNA molecules (100 kb) using simultaneous electrical and optical signal readout. Results of this research will bring about a novel bioanalytical platform that can be used to capture comprehensive genetic data with high temporal resolution. In this research, an integrated nanochannel-nanopore device will be designed and fabricated, wherein nanochannels will be used to unravel the long coiled DNA and feed the stretched molecules into the nanopore, which in turn will be used to discern the structural features of the DNA. The understanding of underlying physics of nanopore translocation of long DNA strands and the ability to control this translocation dynamics will help to realize nanopore based DNA sequencers.