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

在化学系化学测量和成像计划的支持下，Frontiera教授正在开发一种能够探测纳米尺度化学结构的显微成像技术。光学显微镜对于样品的"放大"程度是有限制的，因为光的波动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，在短得多的长度尺度上具有巨大的化学组成变化。这种纳米级的变化导致在药物结合和细胞信号传导等过程中的广泛反应。Frontiera教授的研究涉及光学显微镜技术的开发和应用，该技术能够在纳米长度尺度上检查化学成分。在成功演示该技术后，研究人员计划探测模型细胞膜对药物分子的反应，以了解纳米级变化如何影响功能。这项工作的教育组成部分是让学生领导的教程，预计将说明光谱学和显微镜的先进概念，向公众创建。 这些技术越来越多地用于医疗保健、食品安全、机械加工和制药等领域。此外，Frontiera教授还参加了每年为超过11，000名当地小学生举办的"Energy and U"化学现场推广节目，其中大部分是目前科学界代表性不足的少数民族。该研究项目的重点是开发超分辨率拉曼成像技术，并将其用于确定纳米级局部环境如何影响脂质膜的功能。目前的远场光学显微镜突破了衍射极限，需要用荧光团标记，因此，样品容易降解和变化（因为标记可能会改变系统的结构或动力学）。Frontiera教授和她的团队将受激发射损耗显微镜和飞秒受激拉曼光谱学的联合收割机元素结合起来，创造了一种广泛有用的技术，能够在纳米长度尺度上进行无标记化学成像。该技术的飞秒性质使远场亚衍射探测核运动的时间尺度上的结构变化。为了证明无标记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持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，最终可能适用于生物医学，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。

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.