High Performance Terahertz Spectroscopy Systems for Advanced Biological Studies

用于高级生物学研究的高性能太赫兹光谱系统

• 批准号: 1933554
• 负责人: Mona Jarrahi
• 金额: $ 42.54万
• 依托单位: University of California-Los Angeles
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1933554&HistoricalAwards=false
• 关键词: Performance; Terahertz; Spectroscopy; Systems; Advanced

Near-field microscopy systems such as Scanning Tunneling Microscopy, Atomic Force Microscopy, Scanning Optical Microscopy, and Electron Microscopy can yield highly detailed structural information of biological samples. However, their spectral and operational constraints have limited their use for studying dynamics of biological processes. Alternative single-molecule approaches use various labeling techniques for characterizing structural dynamics of biomolecules. Labeling biomolecules near their active sites can be a major challenge and can affect the natural behavior of molecules in many biological processes. To address these limitations, this project proposes an innovative Scanning Terahertz Nanoscopy system as a powerful label-free biological study tool to advance the research in biophysics. The proposed label-free probing system would allow studying the complex behavior of biomolecules under native conditions, while avoiding exhaustive genetic and biochemical characterization of labeling reactions. The proposed system offers significant flexibility for biological studies in practical settings (flexibility in large area scanning, simultaneous optical excitation, and adding external chemical stimuli) through a fully packaged and fiber-coupled platform. Therefore, the proposed research would benefit the biological research communities conducting research on single-molecule biophysics, cellular structure, nanomedicine, protein folding, etc. As a part of our dissemination, we work closely with the members of the biological research community to utilize and evaluate the developed terahertz spectroscopy system for various biological studies. A special training program is constructed to assimilate graduate students working on this type of interdisciplinary research, undergraduate students and summer interns are recruited for these research activities and special priority is given to recruitment of talented undergraduate and graduate candidates from underrepresented groups. Terahertz waves offer unprecedented functionalities for label-free characterization of biomolecules and studying the structure, dynamics and operation of biological systems. This is because terahertz photon energies are comparable with the low binding energies of molecules inside heavy biomolecules, offering a platform for differentiating proteins and providing information about their conformation states through terahertz spectroscopy. Additionally, since distinct terahertz signatures of biomolecules are dependent on their intermolecular and intramolecular vibrations and rotations, terahertz spectroscopy enables investigating living cells and their interaction inside various biological systems including cell metabolism and reproduction as well as chemical transfer from the environment to cell through cell membrane and possible conformational changes. Moreover, since terahertz spectroscopy can capture femtosecond-scale dynamic variations, it is very well suited for investigating kinetics of molecular motions during protein rearrangement, folding, and binding to other biomolecules. Despite its great promises, the scope and potential use of terahertz technology for biological studies is still limited by low sensitivity and limited spatial resolution of existing terahertz spectroscopy systems. The proposed nanoscopy system solves both limitations, while offering significantly higher sensitivities and bandwidths compared to the state-of-the-art. The proposed time-domain terahertz spectroscopy system consists of a plasmonic photoconductive terahertz source and an electro-optic crystal for broadband terahertz wave generation and detection, respectively. The plasmonic terahertz source and the electro-optic crystal are integrated with a novel terahertz probe, which consists of a tapered waveguide used for focusing the generated terahertz beam onto the biological sample with nanoscale focus dimensions and coupling the reflected terahertz beam from the sample to the electro-optic crystal for detection. The terahertz probe is designed to allow terahertz spectroscopy at the nanoscale without a considerable impact on the spectral bandwidth.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

近场显微镜系统，例如扫描隧道显微镜，原子力显微镜，扫描光学显微镜和电子显微镜可以产生生物样品的高度详细的结构信息。但是，它们的光谱和操作限制限制了它们用于研究生物过程动态的使用。替代单分子方法使用各种标记技术来表征生物分子的结构动力学。在其活性位点附近的生物分子标记可能是一个重大挑战，并且可能会影响分子在许多生物过程中的自然行为。为了解决这些局限性，该项目提出了一种创新的Terahertz纳米镜检查系统，作为一种强大的无标签生物学研究工具，可推进生物物理学研究。提出的无标签探测系统将允许研究天然条件下生物分子的复杂行为，同时避免了标记反应的详尽遗传和生化表征。提出的系统通过一个完全包装和光纤耦合的平台在实用环境中（大面积扫描，同时的光激发和添加外部化学刺激）的生物学研究提供了显着的灵活性。因此，拟议的研究将使进行有关单分子生物物理学，细胞结构，纳米医学，蛋白质折叠等研究的生物学研究群落有益于我们的传播的一部分，我们与生物学研究界成员紧密合作，以利用和利用和使用。评估开发的Terahertz光谱系统，用于各种生物学研究。构建了一项特殊的培训计划，以吸收从事此类跨学科研究的研究生，本科生和暑期实习生的这些研究活动，并特别优先地招募了从代表性不足的人群中招募才华横溢的本科和研究生候选人。 Terahertz波提供了前所未有的功能，用于生物分子的无标签表征并研究生物系统的结构，动力学和操作。这是因为Terahertz光子的能量与沉重生物分子内分子的低结合能相当，它提供了一个平台来区分蛋白质，并通过Terahertz光谱法提供了有关其构象状态的信息。此外，由于生物分子的明显terahertz特征取决于它们的分子间和分子内振动和旋转，因此Terahertz光谱能够研究活细胞及其在各种生物系统中的相互作用，包括细胞代谢和繁殖以及从环境到细胞的化学转移，以及可能的构象变化。此外，由于Terahertz光谱可以捕获飞秒尺度的动态变化，因此非常适合研究蛋白质重排，折叠和与其他生物分子结合期间分子运动动力学。尽管有巨大的承诺，但Terahertz技术在生物学研究中的范围和潜在用途仍然受到现有Terahertz光谱系统的空间分辨率有限的限制。提出的纳米镜检查系统解决了这两个局限性，而与最先进的敏感性和带宽相比，其敏感性和带宽明显更高。所提出的时间域Terahertz光谱系统分别由等离子光导射的光源和用于宽带Terahertz波产生和检测的电晶晶体组成。等离子体terahertz源和电晶晶体与新型的Terahertz探针集成，该探针由用于将产生的Terahertz束聚焦到具有纳米级焦点尺寸的生物样品上的锥形波导，并将样品从样品中耦合到来自样品的Terahertz Beam。电晶晶体可检测。 Terahertz探针旨在允许纳米级的Terahertz光谱法对光谱带宽产生相当大的影响。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的评估标准通过评估来进行评估的。