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(生物科学局)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(工程局)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。这一新工具将在大面积(10平方厘米的S)上产生特征直径为亚微米的寡核苷酸和寡肽的组合阵列。与目前的技术相比，这项工作将在特征大小、生产率和成本方面实现数量级的改进，这些技术提供了进入其他方式无法进行的基础生物学实验的途径，包括在单细胞水平上测量基因或蛋白质表达的新方法。这项开发是一项高度跨学科的努力，结合了化学、材料科学、工程学和纳米技术。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进行暑期实习，以及一系列其他外展活动，涉及芝加哥科学和工业博物馆以提高科学意识，并与突破迈阿密合作为来自经济困难社区的高中生创造实习机会。技术描述：将开发一种工具来创建生物活性分子的超高密度模式，以模拟生物系统的空间和化学复杂性，或创建用于在单细胞水平上确定基因或蛋白质表达的阵列。拟议活动的目标是将新的表面化学与新的仪器能力结合起来，成为原位合成具有特征大小和形状控制平方厘米面积的寡核苷酸或寡肽组合阵列的首选工具。Mirkin和Braunschweig小组最近取得的两项突破性进展使Nanosizer成为可能，即1)开发可单独用光寻址的大规模平行笔阵列，从而将大规模平行笔阵列与光刻(近场和远场)的优点结合起来，以及2)新的表面固定化化学和光化学用于将分子快速打印到表面。该项目将这两个特征结合到一个自动化平台中，该平台可以用可单独寻址的尖端来光激活表面，将其暴露在一系列试剂下，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阵列。当达到适当的仪器仪表里程碑时，将通过机构商业化办公室提交专利申请的初步申请，并将寻求与仪器仪表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，随后在科学期刊上发表完整的报告。当达到重大公共利益的里程碑时，将联系机构公关办公室制作新闻稿。用于制备针尖阵列和微流控单元的光掩模的CAD图纸将在PI的网站上提供，因此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.