NIRT: A Nanometer-Scale Gene Chip

该提案收到于纳米尺度科学与工程计划的响应，NSF 01-157，类别NIRT。随着纳米技术的研究将其小型化和集成的工具扩展到纳米尺度（蛋白质或DNA分子的二级结构的尺度），生物学和信息科学的新前景显露出来，这需要新的多学科研究和教育方法。一个新的问题出现了：生物学能否直接与电子学相结合，从而提供生理学信息？大自然通过离子通道在生物和环境之间提供了一个电子接口，现在可以用纳米技术来模仿。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芯片上的纳米孔机制结合起来，用于探测DNA分子的电活性。最终，这种生物传感器可以快速、廉价地表征最小体积的遗传物质，即单链DNA。一个关键的约束条件是实现所需的灵敏度。为了实现这些目标，一个人工离子通道（AIC）或纳米孔将与一个距离纳米孔一微米内的放大器一起使用，以处理单分子通过通道扩散时产生的高频电信号。具有AIC的膜将浸入缓冲溶液中，DNA分子将被施加的电压偏置推动通过纳米孔，这一原理已在最近的许多实验中得到验证。初步测试已经成功证明，利用高能聚焦电子束，可以在~2-5纳米厚的SiO2膜上重复蚀刻出~2纳米直径的纳米孔。高质量、无针孔的膜被用于这些实验。该项目将开发用于单链DNA超快测序的人工离子通道。AIC装置还将用于直接测量DNA分子的电子输运性质。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产生和修复缺陷的能力有关。此外，使用单个DNA分子作为电子电路的构建块的愿望激发了对其传输特性的探索。到目前为止，DNA的运输特性要么是间接测试，要么是将分子从缓冲溶液中取出并干燥后测试。本文提出的AIC装置将用于直接测量DNA的远程电荷转移，而分子在溶液中保持在其自然环境中。测量结果将与第一性原理原子模拟进行比较。目的是了解控制DNA中电荷传输的基本机制，这一有争议的话题在社区中仍有激烈的争论。

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.