CAREER: Frequency Domain Plasmon Fluctuation Spectroscopy For Single Biopolymer Mechanical Sensing

0953121 Reinhard这份职业建议书描述了一项研究计划，用于开发一种新型等离子体波动光谱学，并将该传感器应用于表征单个生物聚合物的机械性能，而不受观察时间的限制。等离子体激元耦合光谱利用单个贵金属纳米颗粒之间的距离依赖性近场耦合来量化频域中单个生物聚合物中的结构波动。该提案还包含一个强有力的教育部分，描述了培养研究生和本科生以及吸引高中生学习自然科学的计划。迄今为止，贵金属纳米颗粒的单独对之间的等离子体激元耦合（所谓的等离子体激元标尺）已经专门用于时域中的距离测量。在该应用中，该方法被进一步增强以利用单个贵金属纳米颗粒之间的距离依赖性近场相互作用来表征频域中生物聚合物系链中的结构波动。为了实现从时域分析到频域分析的过渡，该项目将开发新一代等离子体规则，检测方法和分析方案。在这个新一代的等离子体统治者的距离相关的等离子体耦合将被系统地映射，提供了新的见解，在0.5 - 30纳米之间的长度尺度的贵金属纳米粒子之间的潜在的电磁相互作用。由此产生的技术将能够分析短（0.5 nm - 30 nm）DNA和RNA的结构波动，而无需施加外力。目标动态距离范围很难用其他传感器解决，但与生物学高度相关。等离子体波动光谱技术能够以高时间分辨率监测该范围内的结构波动，而不受总观察时间的限制，这将有助于更好地了解DNA和RNA在单分子水平上的机械性质，以及这些性质如何随着核蛋白复合物的形成而变化。等离子体激元波动光谱能够以比基于荧光的方法更高的时间分辨率和更长的观察时间分析单个生物聚合物中的结构动力学。该技术将用于研究呼吸道合胞病毒（RSV）核蛋白复合物的力学性质，以揭示病毒转录和复制的基本调控机制。RSV是婴儿细支气管炎的最常见原因，对其转录和翻译的分子理解可以为改进治疗和诊断铺平道路。除了科学影响外，该职业计划还将具有明确的教育和推广效益。该项目将为高中生、本科生和研究生提供参与合作研究和教育计划的机会。拟议努力的跨学科主题领域是广大公众的极大兴趣。与实验室研究协同，该计划将通过主要研究者的年度“纳米营”为当地内城高中的学生（其学生主要来自代表性不足的群体）提供大量的外展服务。为期一周的“夏令营”的目的是让学生体验纳米技术的兴奋，特别是科学的兴奋。主要研究者将赞助本科生和感兴趣的高中生谁已经完成了NanoCamp获得动手研究经验，在拟议的跨学科研究工作。

0953121ReinhardThis CAREER proposal describes a research plan for the development of a novel plasmon fluctuation spectroscopy and for the application of this sensor to characterize the mechanical properties of individual biopolymers without limitation in observation time. Plasmon coupling spectroscopy utilizes the distance-dependent near-field coupling between individual noble metal nanoparticles to quantify structural fluctuations in individual biopolymers in the frequency domain. The proposal also contains a strong educational component describing plans for training graduate and undergraduate students, as well as attracting high-school students to the natural sciences.Intellectual Merit. To date, plasmon coupling between individual pairs of noble metal nanoparticles, so called plasmon rulers, has been exclusively used for distance measurements in the time domain. In this application the method is further enhanced to exploit the distance dependence near-field interactions between individual noble metal nanoparticles to characterize structural fluctuations in the biopolymer tether in the frequency domain. To achieve the transition from a time to a frequency domain analysis, the proposed project will develop a new generation of plasmon rulers, detection approaches, and analysis schemes. The distance dependent plasmon coupling in this new generation of plasmon rulers will be systematically mapped, providing new insights into the underlying electromagnetic interactions between noble metal nanoparticles on length scales between 0.5 - 30 nm. The resulting technology will be able to analyze structural fluctuations in short (0.5 nm - 30 nm) DNAs and RNAs without the need to apply an external force. The targeted dynamic distance range is difficult to address with other sensors but is biologically highly relevant. Plasmon fluctuation spectroscopy's ability to monitor structural fluctuations in this range with high temporal resolution without limitation in total observation time will enable improved insights into the mechanical properties of DNAs and RNAs on the single molecule level and how these properties change as consequence of nucleoprotein complex formation.Broader Impact. Plasmon fluctuation spectroscopy enables the analysis of structural dynamics in individual biopolymers with higher temporal resolution and longer observation time than with fluorescence-based approaches. The technique will be applied to probe the mechanical properties of the nucleoprotein complex of the respiratory syncytial virus (RSV) to reveal the virus' fundamental regulation transcription and replication principles. RSV is the most common cause of bronchiolitis among infants and molecular understanding of its transcription and translation can pave the way to improved therapeutics and diagnostics. In addition to scientific impact, this CAREER plan will also have clear educational and outreach benefits. The project will offer high-school, undergraduate and graduate students the opportunity to participate in a collaborative research and education program. The interdisciplinary subject area of the proposed effort is of great interest to the general public. Synergistically with the laboratory research, the plan will enable a substantial outreach through the Principal Investigator's annual "NanoCamp" for students from local inner city high schools (whose students come primarily from underrepresented groups). The aim of the hands-on, week-long "camp" is to enable students to experience the excitement of nanotechnology in particular and of science in general. The Principal Investigator will sponsor undergraduate students and interested high school students who have completed NanoCamp to obtain hands-on research experience in the proposed interdisciplinary research effort.