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

0651903 Strano，Michael S.单壁碳纳米管（SWNT）是光学传感的理想基底，因为它们具有大的拉曼散射截面和近红外（nIR）光致发光。后者发生在来自生物介质（例如全血）的吸收、散射和自发荧光最小化的情况下。由于电子被限制在一维的圆柱形几何结构中，碳纳米管对它们表面上的分子吸附表现出有趣的敏感性，对几类化学和生物部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领域。我们是第一个创建用于NIR葡萄糖检测的生物医学植入式传感器的公司（Nature Materials 4，86，2005）。我们证明了DNA杂交的光学转导（Nano Letters 6，371，2006）。最近，在开创性的工作中，我们证明了在活细胞中成功操作用于有毒离子检测（Science 311，508，2006）。在这一更新提案中，我们描述了一个在这一新领域继续创新的计划，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。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局限性。我们发现，许多吸附过程涉及DNA/RNA的单壁碳纳米管具有大大增强的热力学屏障自由溶液的值，转化为非常长的转导时间。我们展示了一些成功的建模这些影响，使用曲面上的吸附理论。这些模型将被用来形成假设的长度和顺序的吸附过程的影响，通过实验验证。介电调制是一种新的检测方式，我们已经发现单壁碳纳米管。在此，荧光在DNA杂交时转移到较高的能量，并且当二价金属阳离子被引入时转移到较低的能量，因为SWNT上的表面覆盖度改变。前一种机制仅对（6，5）纳米管起作用，原因是未被覆盖。在此更新计划中，我们还打算将该平台扩展到高灵敏度的DNA基因毒素测量。我们显示的初步数据表明，我们可以测量流量的美法仑，模型遗传毒性剂，在真实的时间内单个活细胞。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破坏活细胞和组织中的DNA。这项工作将推进DNA与其他DNA、蛋白质和聚合物吸附在碳纳米管基底上的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。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。应用包括从强散射、近红外透明介质（如人体）内操作。目标是开发一套新的工程工具，能够用于以前难以处理的光学介质，如全血血清，厚组织和活的，未加工的细胞culture.Broader影响的拟议活动：开发被动的，非侵入性的传感器的病原体识别或医学筛查应用的经济和社会效益是巨大的。想象一下，通过用本提案中概述的nIR荧光团传感器标记选择性结合剂，并用nIR光照射可疑人员或区域，能够筛查个人、衣物和周围环境的天花污染。这种传感技术还将应用于注射、血管或经皮植入物，为医学界提供一种以前所未有的细节远程传感纳米级生化过程的方法。外联工作包括积极参与UIUC的IMPRINT计划，少数民族学生在任期的第一年与研究实验室配对。该项目还将与W。关于工程教育和社会推广问题的哈马克。作为该项目的一部分，还提出了一个基于调查的纳米技术课程。

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.