Nano-Scale Tools for Use in Cell Biology

描述（由申请人提供）：拟议的工作将开发用于表征哺乳动物细胞的纳米级工具;它将最终导致用于药物发现，疾病诊断和研究基础细胞生物学的新工具。其理由是，生物实体的研究基本上涉及细胞的纳米级成分的研究：亚细胞器，病原体，大分子。需要纳米尺度的工具来检查和分析这些成分在亚细胞尺度。该研究将使用“生物友好”纳米技术（软光刻和自组装单层）创建纳米级组件（棒，颗粒和表面），并使用它们来检查哺乳动物细胞。它将使用基于纳米科学的方法：1）创建具有受控形状，分子组成和机械特性的2D和3D微环境用于细胞研究; 2）创建电，光学和机械功能的纳米系统，允许选择性刺激细胞，并允许以亚细胞分辨率读出细胞电，化学和机械响应; 3）利用表现出纳米系统特有的量子现象的系统（例如，超顺磁性、超发光），以产生与生物学相关新的物理学和化学，并利用对物理科学的这种理解提供关于细胞结构和功能的全新类别的信息; 4）开发多路复用纳米级技术的方法，以并行测量具有高统计可靠性的单细胞的功能和特性; 5）使用重要的生物学问题证明这些工具的相关性和应用。这项工作将联合收割机产生一个“纳米工具细胞工作台”;它有四个具体目标：1）创建新型多功能纳米尺度结构、颗粒、组件和表面，以及使用这些实体的分析系统，2）使用纳米工具的这个“工作台”来了解单个细胞如何感知机械线索并将其与化学整合2D和3D微环境中的电信号，3）创建纳米级控制界面，快速启动细胞信号转导和读出生化反应的变化，以及4）将这些纳米技术与微流体系统结合联合收割机，以创建基于集成细胞生物芯片的医疗设备的原型。

DESCRIPTION (provided by applicant): The proposed work will develop nanoscale tools for characterizing the mammalian cell; it will ultimately lead to new tools for drug discovery, diagnosis of disease, and studying fundamental cell biology. Its justification is that study of biological entities fundamentally involves the study of nanoscale components of the cell: subcellular organelles, pathogens, macromolecules. Nanoscale tools are required to examine and analyze these components at the subcellular scale. The research will create nanometer-scale components (rods, particles, and surfaces) using "biology-friendly" nanotechnology (soft lithography and self-assembled monolayers), and use them to examine mammalian cells. It will use nanoscience-based approaches to:1) create 2D and 3D microenvironments with controlled shapes, molecular composition, and mechanical characteristics for studies of cells; 2) create electrically, optically, and mechanically functional nanosystems that permit selective stimulation of cells, and allow read-out of cellular electrical, chemical and mechanical responses with subcellular resolution; 3) leverage systems that exhibit quantum phenomena unique to nanosystems (e.g., superparamagnetism, superluminosity) to generate new physics and chemistry relevant to biology, and use this understanding of physical science to afford fundamentally new classes of information about cell structure and function; 4) develop methods to multiplex nanoscale technologies to measure functions and characteristics of single cells in parallel, with high statistical reliability; 5) demonstrate the relevance and application of these tools using important biological problems. The work will combine to generate a "nanotool cellular workbench"; it has four specific aims: 1) To create novel multifunctional nanometer-scale structures, particles, components, and surfaces, and analytical systems that use these entities, 2) To use this "work bench" of nanotools to understand how individual cells sense mechanical cues and integrate them with chemical and electrical signals in 2D and 3D microenvironments, 3) To create nanoscale control interfaces that rapidly actuate changes in cellular signal transduction and read-out biochemical responses, and 4) To combine these nanotechnologies with microfluidic systems to create prototypes for integrated cellular biochip-based medical devices.