CAREER: Super-resolution Raman microscopy for all-optical, label-free nanoscale chemical imaging

职业：用于全光学、无标记纳米级化学成像的超分辨率拉曼显微镜

• 批准号: 1552849
• 负责人: Renee Frontiera
• 金额: $ 59万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1552849&HistoricalAwards=false
• 关键词: CAREER; Super; resolution; Raman; microscopy

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Frontiera is developing a microscopic imaging technique capable of probing chemical structure on nanometer length scales. Optical microscopes have a limit as to how far one is able to "zoom in" on a sample, as the wavelike nature of light limits the resolution to several hundred nanometers. However, many important structures, such as the surface of living cells, have tremendous variation in chemical composition on much shorter length scales. This nanoscale variation leads to wide range of responses in processes such as pharmaceutical binding and cellular signaling. Professor Frontiera's research entails the development and application of an optical microscopy technique that is capable of examining chemical composition on a nanometer length scale. After the successful demonstration of the technique, the researchers plan to probe the response of model cellular membranes to pharmaceutical molecules, in order to understand how nanoscale variation affects function. The educational component of this work is to have students lead the creation of tutorials that are expected to illustrate advanced concepts in spectroscopy and microscopy, to the public. These techniques are increasingly used in fields as diverse as health care, food safety, machining, and pharmaceutical manufacturing. In addition, Professor Frontiera performs in the "Energy and U" program, a live outreach show about chemistry performed annually for over 11,000 local elementary students, a majority of whom are minorities currently underrepresented in science.This research project is focused on the development of a super-resolution Raman imaging technique and its use in determining how nanoscale local environments affect the function of lipid membranes. Current far-field optical microscopies which break the diffraction limit require labeling with fluorophores, and thus, the samples are prone to degradation and the change (as labeling may change the structure or dynamics of the system). Professor Frontiera and her team combine elements of stimulated emission depletion microscopy and femtosecond stimulated Raman spectroscopy to create a broadly useful technique capable of label-free, chemical imaging on nanometer length scales. The femtosecond nature of the technique enables far-field sub-diffraction probing of structural changes on the timescale of nuclear motion. To demonstrate the applicability of label-free super-resolution Raman imaging, Professor Frontiera and her team determine how nanoscale composition and fluidity of supported lipid membranes are affected by the addition of small molecule pharmaceuticals. This nanoscale imaging technique, which is able to probe how environmental heterogeneities affect function, may ultimately be applicable in areas such as biomedicine, pharmaceutical and food safety, photovoltaic and photocatalytic device characterization, and materials science.

在化学系化学测量和成像项目的支持下，Frontiera教授正在开发一种能够在纳米尺度上探测化学结构的显微成像技术。光学显微镜能够“放大”样品的距离是有限的，因为光的波浪形性质将分辨率限制在几百纳米。然而，许多重要的结构，如活细胞的表面，在更短的长度尺度上具有巨大的化学成分变化。这种纳米级的变化导致了药物结合和细胞信号传导等过程中的广泛反应。Frontiera教授的研究需要开发和应用一种光学显微镜技术，能够在纳米尺度上检查化学成分。在成功演示该技术后，研究人员计划探索模型细胞膜对药物分子的反应，以了解纳米尺度的变化如何影响功能。这项工作的教育部分是让学生领导教程的创作，这些教程有望向公众展示光谱学和显微镜的先进概念。这些技术越来越多地应用于卫生保健、食品安全、机械加工和制药制造等领域。此外，Frontiera教授还在“能源与U”项目中表演，这是一个关于化学的现场推广节目，每年为11,000多名当地小学生表演，其中大多数是目前在科学领域代表性不足的少数民族。本研究项目的重点是超分辨率拉曼成像技术的发展及其在确定纳米尺度局部环境如何影响脂质膜功能方面的应用。目前的远场光学显微镜突破衍射极限，需要用荧光团标记，因此，样品容易降解和变化（因为标记可能改变系统的结构或动力学）。Frontiera教授和她的团队结合了受激发射耗尽显微镜和飞秒受激拉曼光谱的元素，创造了一种广泛有用的技术，能够在纳米尺度上进行无标签的化学成像。该技术的飞秒性质使远场亚衍射探测核运动时间尺度上的结构变化成为可能。为了证明无标签超分辨率拉曼成像的适用性，Frontiera教授和她的团队确定了添加小分子药物如何影响支撑脂质膜的纳米级组成和流动性。这种纳米级成像技术能够探测环境异质性如何影响功能，最终可能应用于生物医学、制药和食品安全、光伏和光催化器件表征以及材料科学等领域。

项目成果

Femtosecond stimulated Raman spectro-microscopy for probing chemical reaction dynamics in solid-state materials

• DOI: 10.1063/5.0009976
• 发表时间: 2020-07-21
• 期刊: JOURNAL OF CHEMICAL PHYSICS
• 影响因子: 4.4
• 作者: Cassabaum, Alyssa A.;Bera, Kajari;Frontiera, Renee R.
• 通讯作者: Frontiera, Renee R.

Stimulated Raman imaging below the diffraction limit with a MHz laser

• DOI: 10.1002/jrs.5970
• 发表时间: 2020-08
• 期刊: Journal of Raman Spectroscopy
• 影响因子: 2.5
• 作者: Christian T. Graefe;David Punihaole;Michael J Lynch;W. R. Silva;R. Frontiera