NER: Integration of Nanoscale Photonics with Silicon MEMS Injector for Studies on the Embryonic Development Through Calibrated Genetic Perturbation

这项研究的目的是将纳米尺度的光子科学和工程与硅上的微电子机械系统(MEMS)相结合，以系统地研究基因功能，并了解对发育和疾病具有重要意义的新的分子机制。这些研究旨在通过高通量RNA干扰(RNAi)显微注射在果蝇自组装胚胎上鉴定从果蝇基因组序列中推断出的新蛋白质的功能。主要包括：(1)基于二维光子晶体的力传感器与硅MEMS注入器集成的设计与制作。力显微镜是由同一个注射器提供的，它带有一个集成的基于悬浮在微悬臂梁上的光子晶体的纳米光子位移传感器。(2)实现大规模并行RNAi微注射的流体自组装的数值和纳米光学表征。智力优势：拟议的纳米级设备和系统架构将可扩展到测试和理解其他模式生物和细胞的发育机制。最终目标是开发纳米级工程活性底物，使有机体(胚胎、细胞和组织)发育具有可控的遗传特征。这项研究的更广泛影响使大规模并行的基础遗传学研究、蛋白质组学以及快速和微型化的药物发现努力成为可能。更广泛的影响：该研究计划还与NSF NER的核心教育倡议相结合，将纳米级光子学、微纳设备、计算和生物化学整合到从单分子到细胞和组织的基础生物学研究中，并应用于改进诊断传感和成像模式。由此产生的研究和教育过程、材料和技术将很容易获得和广泛传播。

The objective of this research is to integrate nano-scale photonic science and engineering with microelectromechanical systems (MEMS) on silicon to systematically study gene functions and to understand new molecular mechanisms that are important for development and disease. The proposed investigations are aimed at identifying, through high-throughput RNA-interference (RNAi) microinjection on self-assembled Drosophila embryos, the functions of the new proteins that have been inferred from the Drosophila genome sequence. The approaches are: (1) Design and fabrication of 2-D photonic crystal based force sensor integrated with a silicon MEMS injector. The force microscopy is provided by the same injector with an integrated nano-photonic displacement sensor based on photonic crystals suspended on micro-cantilevers. (2) Numerical and nano-optical characterization of fluidic self-assembly enabling massively parallel RNAi microinjection. Intellectual Merit:The proposed nanoscale devices and system architecture will be extendable to testing and understanding the mechanics of development of other model organisms and cells. The ultimate goal is the development of nano-scale engineering-active substrates tailoring organism (embryos, cells and tissues) development with controllable genetic characteristics. The broader impact of the research enables massively parallel fundamental genetics research, proteomics, and rapid and miniaturized drug discovery efforts. Broader Impact:The research plan is also synergized with the core educational initiative of NSF NER on integrating nanoscale photonics, micro-nano devices, computing and biochemistry into fundamental biological studies at levels ranging from single molecules, to cells, and tissues, with applications to improve diagnostic sensing and imaging modalities. The resulting research and educational processes, materials and technologies will be readily accessible and widely disseminated.