RNA Nanomotor Based Active Devices for Biology and Medicine

用于生物学和医学的基于 RNA 纳米电机的有源装置

• 批准号: 7278556
• 负责人: Rashid Bashir
• 金额: $ 18.1万
• 依托单位: PURDUE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-03 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7278556
• 关键词: ATP Hydrolysis; ATP phosphohydrolase; Address; Aluminum; Aluminum Oxide; Area; Bacteriophages; Bioelectric Energy Sources; Biological; Biology; Biomedical Technology; Caliber; Capsid; Chemistry; Collection; DNA; DNA Packaging; Deposition; Detection; Development; Devices; Diagnostic; Docking; Drug Metabolic Detoxication; Electron Beam; Engineering; Ensure; Enzymes; Film; Filtration; Fluorescence Microscopy; Generations; Genomics; Hand; Harvest; Health; Health Status; Hybrids; Interdisciplinary Study; Investigation; Light; Liquid substance; Location; Locomotion; Medical Device; Medicine; Membrane; Microbiology; Microfluidics; Molecular Conformation; Molecular Motors; Monitor; Motor; Movement; Nanostructures; Nanotechnology; Nanotubes; Nature; Operative Surgical Procedures; Oxides; Platinum; Play; Power Sources; Principal Investigator; Process; Proteins; Proteomics; Pump; RNA; Range; Research; Research Project Grants; Role; Science; Silicon; Small RNA; Speed; Stress; Structure; Surface; System; Technology; Time; Torque; Viral; base; concept; design; dimer; electrical measurement; electron beam lithography; interdisciplinary approach; lithography; monolayer; nano; nanobiotechnology; nanofabrication; nanomechanics; nanopore; nanoscale; nanosystems; novel; pH gradient; programs; self assembly; sensor; tool; two-dimensional

DESCRIPTION (provided by applicant): Nanotechnology is truly revolutionizing our ability to manufacture and design active devices and systems that are small, cheap, and ultra-sensitive. The need to produce small medical devices for rapid and parallel detection or health monitoring is intensifying. Moreover, as the micro-fabricated devices get smaller and smaller with each new development in materials science and engineering, the need to design and fabricate biologically inspired nanoscale devices and sensors and ultra-compact power sources to drive these devices and sensors are emerging. Nature can provide the tools to address the above needs. Molecular motors, such as ATPase [Noji et al., 1997], bacterial flagellar [Sowa et al., 2005], or viral DNA packaging motors [Guo, 2002; Shu et al., 2003] can be utilized to synthesize power at the nano-scale. Some of these motors can generate force up to tens or hundreds of pico Newtons. Some of them can use energy and generate force, via ATP hydrolysis, or use the force and generate energy in the form of ATP, via electrolocomotive force or pH gradients, with efficiencies in the range of 80-100% [Yasuda et al., 2001; Aksimentiev et al., 2004]. Some of these motors can have rotational speeds of 100-1000 rpm [Sowa et al., 2005]. In the recent years, nanofabrication capabilities have progressed to a point where sub 20nm nanopores, nanowires, and nanotubes can be grown at specific locations on a silicon wafer such that these structures can possibly be interfaced with biological motors for applications such as nanomechanics, filtration, locomotion, and energy generation and harvesting. In this project, we propose to develop active nanostructures and systems based on biological nanomotors. Our focus here would be the use of the bacteriophage phi29 DNA packaging nanomotor that is driven and geared by small RNA molecules termed packaging RNA or "pRNA". This nanomotor has been shown to play a novel and essential role in transporting phi29 genomic DNA into procapsids. As more progress is made in understanding the structure and mechanisms of these novel systems, it is time to evaluate these structures using bionanotechnology-based approaches and to explore the interface between these nanomotors and synthetic structures using top down and bottoms up fabrication technology to form active nanostructures and nanosystems. Our core platform will consist of the pRNA-driving motors anchored on nanoporous membranes on micromachined silicon or Alumina based membrane via a 2-dimensional self- assembled DNA crystal. The use of the DNA self assembled layer will ensure the integrity and functionality of the nanomotor. The development and characterization of this basic platform is a significant challenge in itself and requires a cohesive interdisciplinary approach. We will integrate the nanomotor in a hybrid silicon based device and demonstrate its operation, and then integrate the nanomotor without the capsid and demonstrate the translocation of dsDNA through the motor. Once these tasks are accomplished, it will be possible to investigate various technology modules such as active pumping surfaces within microfluidic channels, active sieving and filtration, and many other applications directly relevant to biology and medicine.

描述（由申请人提供）：纳米技术确实彻底改变了我们制造和设计小型，便宜且超敏感的主动设备和系统的能力。生产小型医疗设备以快速和并行检测或健康监测的需求正在加剧。此外，随着材料科学和工程领域的每一个新开发的微型设备的越来越小，需要设计和制造具有生物学启发的纳米级设备和传感器以及超紧凑型电源来驱动这些设备和传感器。大自然可以提供满足上述需求的工具。分子电动机，例如ATPase [Noji等，1997]，细菌鞭毛[Sowa等，2005]或病毒DNA包装电动机[Guo，2002; Shu等，2003]可以用于合成纳米级的功率。这些电动机中的一些可以产生数十或数百个Pico Newton的力。其中一些可以通过ATP水解使用能量并产生力，或者使用该力并以ATP形式产生能量，通过电求解力或pH梯度，其效率在80-100％的范围内[Yasuda等，2001; Aksimentiev等，2004]。这些电动机中的一些可以具有100-1000 rpm的旋转速度[Sowa等，2005]。近年来，可以在硅晶片上的特定位置种植纳米型功能，直到20nm纳米孔，纳米线和纳米管都可以生长，以便这些结构可以与纳米力学，滤液，滤液，滤液，现场和能量，现场和能量，现代和能量，现场和生成和生成和纳米机械的生理电动机相连。在这个项目中，我们建议基于生物纳米运动器开发活跃的纳米结构和系统。我们在这里的重点是使用噬菌体PHI29 DNA包装纳米动物，该纳米动物由称为包装RNA或“ PRNA”的小RNA分子驱动和齿轮。该纳米能力已被证明在将PHI29基因组DNA转运到procapsids中起着新颖而重要的作用。随着在理解这些新型系统的结构和机制方面取得了更大的进步，现在是时候使用基于Bionanotechnology的方法来评估这些结构，并使用自上而下和自下而上的制造技术探索这些纳米运动和合成结构之间的接口，以形成活跃的纳米结构和纳米系统。我们的核心平台将包括通过二维自组装的DNA晶体锚定在微机械硅或氧化铝膜上的纳米多孔膜上的PRNA驱动电动机。 DNA自组装层的使用将确保纳米运动的完整性和功能。这个基本平台的发展和表征本身就是一个重大挑战，需要一种凝聚力的跨学科方法。我们将在基于混合硅的设备中整合纳米运动，并演示其操作，然后在没有衣壳的情况下集成纳米能力，并证明DSDNA通过电机的易位。一旦完成这些任务，就可以研究各种技术模块，例如微流体渠道内的主动泵送表面，主动筛分和过滤，以及许多与生物学和医学直接相关的其他应用。