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

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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.