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

点击翻译按钮获取中文摘要

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.