Nano-Scale Tools for Use in Cell Biology

用于细胞生物学的纳米级工具

• 批准号: 7629029
• 负责人: GEORGE M WHITESIDES
• 金额: $ 41.27万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7629029
• 关键词: Apoptosis; Applications Grants; Area; Belief; Biochemical; Biochemistry; Biocompatible; Biological; Biology; Biosensor; Boston; Cell Shape; Cell Size; Cells; Cellular Structures; Cellular biology; Characteristics; Chemicals; Chemistry; Clinical Medicine; Cues; Detection; Development; Devices; Diagnostic; Dimensions; Event; Exhibits; Future; Gene Expression; Individual; Laboratories; Lead; Length; Life; Magnetism; Mammalian Cell; Measures; Mechanics; Medical; Medical Device; Methods; Microfluidics; Molecular; Nanotechnology; Optics; Organelles; Pathology; Pediatric Hospitals; Physics; Positioning Attribute; Process; Reading; Research; Resolution; Sensory; Signal Transduction; Structure; Surface; System; Technology; Therapeutic; Tissues; Transduction Gene; User-Computer Interface; Work; base; biochip; cell behavior; cell growth; cell motility; directional cell; disease diagnosis; drug discovery; information processing; insight; lithography; macromolecule; medical schools; millimeter; millisecond; molecular shape; monolayer; nanoparticle; nanoscale; nanoscience; nanosystems; nanotool; novel; particle; pathogen; physical science; prototype; quantum; response; retinal rods; study characteristics; tool

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.

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尺度工具；它最终将为药物发现、疾病诊断和基础细胞生物学研究带来新的工具。其理由是，对生物实体的研究从根本上涉及对细胞的纳米级成分的研究：亚细胞细胞器、病原体、大分子。需要纳米级的工具在亚细胞尺度上检查和分析这些成分。这项研究将使用“生物友好”的纳米技术（软光刻和自组装单层）制造纳米级组件（棒、颗粒和表面），并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)创建具有可控形状、分子组成和机械特性的二维和三维微环境，用于细胞研究；2)创造电、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、化学和机械反应；3)利用纳米系统特有的量子现象（例如，超顺磁性，超光度）来产生与生物学相关的新物理和化学，并利用这种对物理科学的理解来提供关于细胞结构和功能的基本新类别的信息；4)发展多重纳米技术的方法，以并行测量单细胞的功能和特性，具有较高的统计可靠性；5)通过重要的生物学问题展示这些工具的相关性和应用。这项工作将结合起来产生一个“纳米工具细胞工作台”；它有四个具体目标：1)创建新的多功能纳米级结构、粒子、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“工作台”来了解单个细胞如何感知机械信号，并将其与二维和三维微环境中的化学和电信号相结合；3)创建纳米级控制接口，快速启动细胞信号转导的变化并读出生化反应。4)将这些纳米技术与微流体系统结合起来，创造基于集成细胞生物芯片的医疗设备的原型。