Programmable micro/nano-fluidic based platform for high-throughput and large scale single-molecule analysis

这项研究计划的愿景是设计基于微/纳米流体的尖端技术，以促进我们接触和探索单生物分子功能中的罕见事件的能力。单分子分析是一种强大的方法，它可以提供前所未有的生物医学信息的新细节，这是使用传统平均技术无法实现的。它有助于我们理解复杂的生物过程(例如癌症等疾病)，在这些过程中，需要在单个细胞提取的单个分子水平上识别蛋白质、DNA、RNA的功能特征。一个可编程的、高效的、一次性的和微型的“智能”系统可以极大地改进我们感兴趣的地点可以访问的生物分析。高效的样品处理、隔离、吞吐量、可配置性和大规模分析能力是这种智能小型化实验室芯片系统的关键。这项研究计划将首次通过协同结合3D制造样品机械手和基于可编程液滴的微流控技术来创新“智能”微/纳米流体技术。基于三维特征的样品机械手可以增强对单个生物分子的捕获、分离和转移能力。此外，可编程微流体允许通过实时传感和控制集成芯片上的决策能力。从工程学和基础科学的角度来看，这项研究将解决一些基本问题，包括：在玻璃上的三维微/纳米制造，生物分子在微/纳米尺寸三维几何结构中的传输，分子在不同纳米约束下的力学行为，以及利用纳米电润湿技术进行生物分子的传输和控制。*我的第一个目标是创造一种用于生物分子操纵的高纵横比、高精度微/纳米特征的3D制造方法。3D特征，如改进的通道、连续限制、柱阵列、漏斗和钻石，用于DNA解缠、线性化和移位。传统的制作方法基于干/湿法化学刻蚀，具有较高的粗糙度、有限的纵横比和特征质量。在这项研究中，我们将探索一种新的基于玻璃热变形的三维制作方法。的第二个目标是将可编程射流与3D微/纳米功能相结合。基于可编程液滴的流动将首次与连续限制纳米流体相结合，以实现高通量、快速和大规模的单分子分析。这一计划的广泛影响提供了许多有吸引力的应用，包括医疗保健、疾病诊断、药物发现、环境安全、农业和基础研究。

The vision of this research program is to engineer micro/nano-fluidic based incisive technologies that would facilitate our ability to reach and explore rare events in single biomolecular functionalities. Single molecule analysis is a powerful approach that allows unprecedented new details of biomedical information, which are not possible using conventional averaging techniques. It facilities in our understanding of complex biological process (for example diseases like Cancer), where it is necessary to identify the functional characteristics of protein, DNA, RNA at single molecule level extracted from a single cell. A programmable, efficient, disposable, and miniature "smart" system can dramatically improve biological analysis accessible at our point-of-interest. Efficient sample manipulation, isolation, through-put, configurability and large-scale analysis capability are the key for such smart miniaturized lab-chip system. This research program would for the first time innovate "smart" micro/nano-fluidic technologies via synergistically combining 3D fabricated sample manipulator with programmable droplet based microfluidics. 3D feature based sample manipulator can enhance the ability to capture, isolate and translocate single biomolecules. Additionally, programmable microfluidics allows integrating on-chip decision-making capability via real-time sensing and controls. From the engineering and basic science point of view, the research will address a number of fundamental questions including: 3D micro/nano fabrication on glass, transport of bio-molecules through micro/nanometer-size 3D geometries, mechanical behavior of molecules at varying nano-confinement, and biomolecules transport and controls using nano-electrowetting. ***My first objective is to create a 3D fabrication method with high-aspect ratio and high precision manufacturing of micro/nano-features for biomolecule manipulation. 3D features such as modified channel, continuous confinement, post arrays, funnels, and diamonds are used for DNA untangling, linearization and translocation. Conventional fabrication methods are based on dry/wet chemical etching, that has higher roughness, limited aspect ratio and feature quality. In this research, 3D fabrication by using a new method based on thermal shape deformation of glass will be pursued. The second objective of is to integrate programmable fluidics with 3D micro/nano-features. Programmable droplet based flows will be first time combined with continuous confinement nano-fluidics for achieving high-throughput, faster and large scale single molecule analysis. The wide implication of this program offers many attractive applications including health care, disease diagnostics, drug discovery, environmental security, agriculture and basic research.**