Collaborative Research: IDBR: Type A: The Nanosizer: A New Tool for the Photochemical Fabrication of Bioactive Nanoarrays

该奖项由两个项目联合颁发-（1）生物基础设施司（生物科学理事会）的生物研究仪器开发，以及（2）化学，生物工程，环境和运输系统司（工程理事会）的纳米生物传感。非技术描述：西北大学和迈阿密大学的研究人员将开发一种仪器来生产生物活性探针的纳米阵列。这种新的工具将产生组合阵列的寡核苷酸和寡肽与亚微米特征直径在大面积（10平方厘米）。这项工作将在特征尺寸、生产率和成本方面实现数量级的改进，从而提供无法以其他方式进行的基础生物学实验，包括在单细胞水平上测量基因或蛋白质表达的新方法。该开发是一项高度跨学科的工作，结合了化学，材料科学，工程和纳米技术。项目活动还将包括为少数民族服务的四年制大学的本科生提供暑期实习机会，以及一系列其他外联活动，这些活动涉及芝加哥的科学与工业博物馆，以促进科学意识，并与突破迈阿密合作，为经济困难社区的高中生创造实习机会。技术说明：将开发一种创造生物活性分子超密度模式的仪器，以模拟生物系统的空间和化学复杂性，或创建用于确定生物活性分子的阵列。基因或蛋白质在单细胞水平上的表达。拟议活动的目标是将新的表面化学与新的仪器功能相结合，以使其成为原位合成寡核苷酸或寡肽组合阵列的首选工具，这些寡核苷酸或寡肽具有平方厘米面积上的特征尺寸和形状控制。Nanosizer是由Mirkin和布伦瑞克集团最近出现的两个突破性进展实现的，即，1）开发可通过光单独寻址的大规模并行笔阵列，从而将大规模并行笔阵列的优点与光刻相结合（近场和远场），和2）用于将分子快速印刷到表面上的新的表面固定化化学和光化学。该项目将这两个功能结合到一个自动化平台中，该平台可以用可单独寻址的尖端光活化表面，将其暴露于一系列试剂，并重复几个循环，以在表面上创建生物活性分子的空间编码组合阵列或纳米粒子。当达到适当的仪器里程碑时，将通过机构商业化办公室进行专利申请的初步提交，并寻求与仪器制造商的合作伙伴关系。研究结果将通过会议进行早期传播，随后在科学期刊上发表全面报告。当达到公众重大关注的里程碑时，将与各机构的公共关系办公室联系，编写一份新闻稿。用于制备尖端阵列和微流体细胞的光掩模的CAD图纸将在PI的网站上提供，以便研究人员可以在现有的AFM上实现Nanosizer。

This award is being made jointly by two Programs- (1) Instrument Development for Biological Research, in the Division of Biological Infrastructure (Biological Sciences Directorate), and (2) Nano-Biosensing, in the Division of Chemical, Bioengineering, Environmental and Transport Systems (Engineering Directorate). Non Technical Description:Researchers at Northwestern University, and the University of Miami will develop an instrument to produce nanoarrays of biologically active probes. This new tool will produce combinatorial arrays of oligonucleotides and oligopeptides with sub-micrometer feature diameters over large areas (10's of square centimeters). The work will achieve order of magnitude improvements in feature size, production rate, and cost over current technologies providing access to fundamental biological experiments that could not otherwise be undertaken, including new ways to measure gene or protein expression at the single cell level. The development is a highly interdisciplinary effort which combines chemistry, materials science, engineering, and nanotechnology. Project activities will also include summer internships for undergraduates from minority-serving four year colleges, and a range of other outreach activities involving the Museum of Science and Industry in Chicago to promote scientific awareness, and with Breakthrough Miami to create internship opportunities for high school students from financially disadvantaged communities.Technical Description:An instrument to create ultradense patterns of biologically active molecules will be developed to model the spatial and chemical complexity of biological systems or create arrays for determining gene or protein expression at the single-cell level. The goal of the proposed activity is to combine new surface chemistries with new instrument capabilities to make a go-to tool for the in situ synthesis of combinatorial arrays of oligonucleotides or oligopeptides with feature size and shape control over square centimeter areas The Nanosizer is enabled by two breakthrough advances to recently emerge from the Mirkin and Braunschweig groups, namely 1) the development of massively parallel pen arrays that are individually addressable by light, thereby combining the advantages of massively parallel pen arrays with photolithography (near- and farfield), and 2) new surface immobilization chemistries and photochemistries for the rapid printing of molecules onto surfaces. This project combines these two features into an automated platform that can photoactivate a surface with individually addressable tips, expose it to a range of reagents, and repeat for several cycles to create spatially encoded combinatorial arrays or nanopatterns of biologically active molecules on surfaces. When the appropriate instrumentation milestones are reached, initial filings of patent applications will be made through institutional commercialization offices, and partnerships will be sought with instrumentation manufacturers. Early dissemination of the research findings will occur through conferences followed by full reports in scientific journals. When milestones of significant public interest are reached, institutional public relations offices will be contacted to produce a press release. CAD drawings for photomasks for preparing tip arrays and microfluidic cells will be made available on the websites of the PIs so researchers can implement the Nanosizer on existing AFMs.