Near Infrared Fluorescent Single Walled Carbon Nanotubes as Novel Solution Phase Optical Sensing Materials - Proposal Renewal

[651903] strano, Michael s .单壁碳纳米管（SWNT）由于其大的拉曼散射截面和近红外（nIR）光致发光，是光学传感的理想衬底。后者发生在生物介质（如全血）的吸收、散射和自身荧光最小的地方。由于电子被限制在一维圆柱形几何结构中，碳纳米管对其表面的分子吸附表现出有趣的敏感性，对几种化学和生物成分产生相当大的响应。单壁碳纳米管的光学调制是我们在过去三年的项目中独家开创的一个领域。我们是第一个创造用于近红外葡萄糖检测的生物医学植入式传感器（Nature Materials 4,86, 2005）。我们展示了DNA杂交的光学转导（纳米快报6,371,2006）。最近，在开创性的工作中，我们展示了在活细胞中检测有毒离子的成功操作（Science 311, 508, 2006）。在这一更新建议中，我们通过研究信号转导的基本机制，并利用工程原理进一步开发这些技术，描述了在这一新领域的持续创新计划。更新计划将回答有关这些系统的核心问题，并解决我们研究中发现的主要限制。我们发现许多涉及DNA/RNA在SWNT上的吸附过程比自由溶液值具有显著增强的热力学障碍，这转化为极长的转导时间。我们展示了一些成功的模拟这些影响使用理论的多电解质吸附在曲面上。这些模型将用来形成关于长度和序列对吸附过程影响的假设，并通过实验验证。介质调制是我们为SWNT发现的一种新的检测方式。在这里，当DNA杂交时，荧光转移到更高的能量，当引入二价金属阳离子时，随着SWNT表面覆盖范围的改变，荧光转移到更低的能量。前一种机制仅适用于（6,5）纳米管，原因尚不清楚。在此更新计划中，我们还打算将该平台扩展到具有高灵敏度的dna基因毒素测量。我们展示的初步数据表明，我们可以在单个活细胞内实时测量梅尔法兰（一种模型基因毒性剂）的通量。想象一下，有一种通用的检测方法能够表明环境中的未知物质是否会立即损害活细胞和组织中的DNA。这项工作将促进对碳纳米管基质上DNA与其他DNA、蛋白质和聚合物吸附物相互作用的科学理解。拟议活动的智力价值：拟议的研究更新将继续推进对以碳为模型系统的一维量子纳米管的电子转移和诱导介电调制的科学理解。在这项工作中探索的科学将产生对环境重要分析物具有高灵敏度和选择性的光学查询传感器分子。应用范围包括从强散射、近红外等透明介质内操作人体。目标是一套新的工程工具，能够用于以前难以处理的光学介质，如全血清、厚组织和活的、未经处理的细胞培养。拟议活动的更广泛影响：开发用于病原体识别或医疗筛查应用的被动、非侵入性传感器的经济和社会效益是巨大的。想象一下，通过在本提案中概述的近红外荧光团传感器上标记选择性结合剂，并用近红外光照射可疑的人或区域，就可以筛查个人、衣服和周围环境中的天花污染。这种传感技术还将应用于注射、血管或透皮植入，为医学界提供一种远程手段，以前所未有的细节在纳米尺度上传感生化过程。拓展工作包括积极参与伊利诺伊大学加州分校的IMPRINT项目，在该项目中，少数族裔学生在其任期的第一年与研究实验室配对。该项目还将与W. Hammack在工程教育和社会推广方面进行合作。本计划亦建议开设一门以探究为基础的纳米技术课程。

0651903Strano, Michael S.Single-walled carbon nanotubes (SWNT) are ideal substrates for optical sensing, due to their large Raman scattering cross-sections and photoluminescence in the near infrared (nIR). The latter occurs where absorption, scattering, and auto-fluorescence from biological media such as whole blood, are minimized. Because the electrons are confined in a one dimensional, cylindrical geometry, carbon nanotubes exhibit intriguing sensitivity to molecular adsorption on their surface, yielding sizable responses for several classes of chemical and biological moieties. The optical modulation of single walled carbon nanotubes is an area that we have pioneered exclusively over past three year project. We were the first to create biomedical implantable sensors for nIR glucose detection (Nature Materials 4, 86, 2005). We demonstrated optical transduction of DNA hybridization (Nano Letters 6, 371, 2006). Recently, in pioneering work, we demonstrated successful operation in live cells for toxic ion detection (Science 311, 508, 2006). In this renewal proposal, we describe a program of continued innovation in this new area by investigating fundamental mechanisms of signal transduction, and using engineering principles to further develop these technologies. The renewal program will answer central questions regarding these systems, and solve major limitations uncovered in our research. We find that many adsorption processes involving DNA/RNA on SWNT possess substantially enhanced thermodynamic barriers over free solution values which translate into exceedingly long transduction times. We show some success in modeling these effects using the theory of polyelectrolyte adsorption on curved surfaces. These models will be utilized to form hypotheses about the influence of length and sequence on adsorption processes to be validated by experiment. Dielectric modulation is a new modality of detection we have uncovered for SWNT. Here, the fluorescence is shifted to a higher energy upon DNA hybridization, and to a lower energy when divalent metal cations are introduced as the surface coverage on the SWNT is changed. The former mechanism is operative only for the (6,5) nanotube for a reason to be uncovered. In this renewal program, we also intend to extend this platform to the measurement of DNA-genotoxins with high sensitivity. We show preliminary data indicating that we can measure the flux of melphalan, a model genotoxic agent, in real time within single living cells. Imagine a universal assay capable of indicating whether an unknown agent in the environment can immediately damage DNA within live cells and tissues. This work will advance the scientific understanding of DNA interactions with other DNA, proteins and polymer adsorbates on carbon nanotube substrates.Intellectual Merit of Proposed Activity: The proposed research renewal will continue to advance the scientific understanding of electron transfer and induced dielectric modulation of 1-D quantum nanotubes using carbon as a model system. The science explored in this work will produce optically-queried sensor molecules with high sensitivity and selectivity for environmentally important analytes. Applications include operation from within strongly scattering, near-infrared transparent media such as the human body. The goal is a new set of engineering tools that have the ability to be used in previously intractable optical media such as whole blood serum, thick tissue and live, unprocessed cell cultures.Broader Impacts of the Proposed Activity: The economic and societal benefits of developing passive, noninvasive sensors for pathogen recognition or medical screening applications are enormous. Imagine being able to screen individuals, clothing and the surrounding environment for small pox contamination by labeling a selective binding agent with a nIR fluorophore sensor as outlined in this proposal and irradiating the suspected person or area with nIR light. This sensing technology will also find applications as injectable, vascular or trans-dermal implants, giving the medical community a remote means of sensing biochemical process at the nanoscale with unprecedented detail. Outreach efforts include active participation with the IMPRINT program at UIUC, where minority students are paired with research labs in the first year of their tenure. The project will also work with W. Hammack on issues of engineering education and societal outreach. An inquiry-based nanotechnology course is also proposed as part of this project.