NIRT: A Nanometer-Scale Gene Chip

NIRT：纳米级基因芯片

• 批准号: 0210843
• 负责人: Gregory Timp
• 金额: $ 130万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-15 至 2006-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0210843&HistoricalAwards=false
• 关键词: NIRT; Nanometer; Scale; Gene; Chip

Timp, GregoryCCR-0210843This proposal was received in response to the Nanoscale Science and Engineering initiative, NSF 01-157, category NIRT. As research in nanotechnology extends its tools for miniaturization and integration to nanometer dimensions (the scale of the secondary structure in a protein or a DNA molecule), new vistas in biology and information science are revealed, which require new multi-disciplinary approaches to both research and education. One new question that emerges is: Can biology be directly integrated with electronics to provide information on physiology? Nature has provided an electrical interface between biology and the environment through ion channels that can now be mimicked using nanotechnology.The main objective of this project is to develop a revolutionary type of silicon integrated circuit that incorporates Metal-Oxide-Semiconductor technology with an on-chip nanopore mechanism for probing the electrical activity of DNA molecules. Ultimately, this biosensor might enable fast, inexpensive characterization of the minimum volume of genetic material, a single strand of DNA. A key constraint is to achieve the required sensitivity. To accomplish these goals, an artificial ion channel (AIC) or nanopore, will be used in conjunction with an amplifier built within one micron from the nanopore, in order to process high-frequency electrical signals occurring when single molecules diffuse through the channel. A membrane having an AIC will be immersed into a buffer solution, and DNA molecules will be pushed through the nanopore by the applied voltage bias a principle that has been tested in a number of recent experiments. Preliminary tests have already successfully demonstrated that ~2-nm diameter nanopores can be reproducibly etched through a ~2-5-nm-thick SiO2 membrane, using a high energy focused electron beam. High-quality, pinhole-free membranes are being used in these experiments. The project will develop artificial ion channels for ultrafast sequencing of single DNA strands. The AIC devices will also be applied for direct measurements of electronic transport properties of DNA molecules. This subject is important since the charge migration in DNA has been linked to the DNA ability to develop and repair defects while being exposed to ionizing radiation. Also, the desire of using single DNA molecules as building blocks for electronic circuits motivates the quest for understanding its transport properties. So far transport properties of DNA have been tested either indirectly or when the molecule is removed from the buffer solution and dried. The AIC device proposed here will be applied to measure directly the long-range charge transfer along DNA, while the molecule is kept in its natural environment in solution. The measurements will be compared with first-principle atomistic simulations. The objective is to understand basic mechanisms that control the charge transport in DNA this controversial topic continues to be strongly debated in the community.

Timp, GregoryCCR-0210843此提案是为了响应纳米科学与工程倡议、NSF 01-157、NIRT 类别而收到的。 随着纳米技术研究将其小型化和集成工具扩展到纳米尺寸（蛋白质或 DNA 分子二级结构的尺度），生物学和信息科学的新前景被揭示，这需要新的多学科方法进行研究和教育。 出现的一个新问题是：生物学能否直接与电子学集成以提供生理学信息？大自然通过离子通道在生物和环境之间提供了电接口，现在可以使用纳米技术进行模拟。该项目的主要目标是开发一种革命性的硅集成电路，该电路将金属-氧化物-半导体技术与片上纳米孔机制相结合，用于探测 DNA 分子的电活动。最终，这种生物传感器可能能够快速、廉价地表征最小体积的遗传物质（单链 DNA）。一个关键的限制是达到所需的灵敏度。为了实现这些目标，人工离子通道（AIC）或纳米孔将与在距纳米孔一微米内构建的放大器结合使用，以便处理单分子扩散通过通道时产生的高频电信号。将具有 AIC 的膜浸入缓冲溶液中，DNA 分子将通过施加的电压偏压推动穿过纳米孔，这一原理已在最近的许多实验中得到测试。初步测试已经成功证明，使用高能聚焦电子束可以通过约 2-5 纳米厚的 SiO2 膜可重复地蚀刻约 2 纳米直径的纳米孔。这些实验中使用的是高质量、无针孔的膜。该项目将开发用于单 DNA 链超快测序的人工离子通道。 AIC 设备还将用于直接测量 DNA 分子的电子传输特性。这个课题很重要，因为 DNA 中的电荷迁移与 DNA 在暴露于电离辐射时形成和修复缺陷的能力有关。此外，使用单个 DNA 分子作为电子电路构建模块的愿望也激发了人们对其传输特性的探索。迄今为止，DNA 的转运特性已通过间接测试或当分子从缓冲溶液中取出并干燥时进行测试。这里提出的 AIC 装置将用于直接测量沿 DNA 的长距离电荷转移，同时分子保持在溶液中的自然环境中。测量结果将与第一原理原子模拟进行比较。目的是了解控制 DNA 电荷传输的基本机制，这个有争议的话题在社区中仍然存在激烈争论。