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)生物基础设施部（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、环境和运输系统部（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，用于生产生物活性探针的纳米阵列。这种新工具将在大范围内（10平方厘米）产生亚微米特征直径的寡核苷酸和寡肽组合阵列。与现有技术相比，这项工作将在特征尺寸、生产速度和成本方面实现数量级的改进，为无法进行的基础生物学实验提供了途径，包括在单细胞水平上测量基因或蛋白质表达的新方法。这一发展是一项高度跨学科的努力，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族裔服务的四年制大学的本科生提供暑期实习机会，以及一系列其他外展活动，包括芝加哥科学与工业博物馆（Museum of Science and Industry），以提高科学意识，以及与Breakthrough Miami合作，为经济困难社区的高中生创造实习机会。技术描述：将开发一种仪器，用于创建生物活性分子的超密集模式，以模拟生物系统的空间和化学复杂性，或创建用于确定单细胞水平基因或蛋白质表达的阵列。提议的活动的目标是将新的表面化学与新的仪器功能相结合，使其成为原位合成寡核苷酸或寡肽组合阵列的专用工具，其特征尺寸和形状控制在平方厘米范围内。纳米尺寸是由米尔金和布伦瑞克团队最近出现的两项突破性进展实现的，即1)开发大规模平行笔阵列，可通过光单独定位；因此结合了大规模平行笔阵列与光刻（近场和远场）的优点，以及2)新的表面固定化化学和光化学，用于在表面上快速打印分子。该项目将这两个特征结合到一个自动化平台中，该平台可以光激活具有单独可寻址尖端的表面，将其暴露在一系列试剂中，并重复几个周期，以在表面上创建空间编码的组合阵列或生物活性分子的纳米模式。当达到适当的仪器里程碑时，将通过机构商业化办公室提交专利申请的初始文件，并寻求与仪器制造商的合作伙伴关系。研究成果的早期传播将通过会议进行，然后在科学期刊上发表全文报告。当重大公共利益达到里程碑时，将联系机构公关办公室制作新闻稿。用于制备尖端阵列和微流体细胞的光罩的CAD图纸将在pi的网站上提供，以便研究人员可以在现有的原子力显微镜上实现纳米尺寸。

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.