SBIR Phase I: Instrumentation for Controlled Fabrication & Characterization of Nanostructures: Assembly of 2-D Membrane Protein Crystals

这个小企业创新研究第一阶段项目将开发一种技术，该技术将允许晶体和其他有序的微纳米结构在液体上以快速和可控的方式生长。该技术将与实时数字成像激光荧光显微镜相结合，以便在整个制造过程中对结构形成进行现场表征。机器人薄膜转移系统的使用有助于制备用于原子分辨率测量的样品，例如电子和扫描探针显微镜。这些改进将大大提高现有技术的水平。第一阶段的实验程序解决了一种新的、简单的、快速的制备膜跨越蛋白有序二维晶体的方法。与传统技术不同，这种新工艺允许实验参数的变化，以促进晶体的制造，既长又短的取向顺序，适合高分辨率的晶体学分析。此外，该过程比传统技术快了几个数量级，并保持了膜蛋白的天然不对称性。该项目的成功将首次为膜蛋白结晶提供一种通用的方法。这可能导致具有重要生物技术意义的新发现，因为原子分辨率的结构信息对于阐明关键膜蛋白的作用机制，从而了解疾病的性质和开发更有效的药物是必不可少的。该技术的独特性能特征提供了许多当前和潜在的应用，从微电子到生物技术等领域。在生物技术领域，这项技术有潜力开发更有效的药物或筛选药物。其他应用包括制造技术上有用的桶状微结构，可以用作控制药物递送的微瓶，以及在遗传筛选中用于将DNA/RNA固定在新材料上。＊＊＊

*** 9661765 Mojtabai This Small Business Innovation Research Phase I project will develop a technology that will allow the growth of crystals and other ordered micro- and nano-structures on a liquid in a fast and controlled fashion. The technology will be integrated with real-time digital imaging laser fluorescence microscopy to allow for in-situ characterization of structure formation, throughout the fabrication process. The use of a robotics film transfer system facilitates preparation of specimens for use in atomic resolution measurements such as electron and scanning probe microscopies. These modifications will substantially improve the existing state-of-the-art of the technology. The experimental program in Phase I addresses a new, simple and fast process for fabrication of ordered two-dimensional crystals of membrane spanning proteins. Unlike conventional techniques, this new process allow for variation of the experimental parameters to facilitate fabrication of crystals with both long- as well as short-range orientation order, suitable for high-resolution crystallographic analysis. In addition, the process is orders of magnitude faster than conventional techniques, and maintains the native asymmetry of the membrane protein. The success of the program will provide, for the first time, a general approach for crystallizing membrane proteins. This may lead to new discoveries of significant biotechnological importance, since structural information at atomic resolution is indispensable for elucidation of the mechanism of action of key membrane proteins, and thereby understanding the nature of disease and for developing more effective drugs. The unique performance characteristics of the technology provide many present and potential applications which range from fields such as microelectronics to biotechnology. In biotechnology the technology has potential for developing more effective drugs, or screening drugs. Other applications include fabrication of technologically useful tub ular microstructures that can be used as micro-vials for controlled delivery of drugs, and for immobilization of DNA/RNA on new materials for use in genetic screening. ***