[IEEE 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Munich, Germany (2019.6.23-2019.6.27)] 2019 Conference on Lasers and Electro-Optics Europe & European Quantum Electronics Conference (CLEO/Europe-EQEC) - Quantitative Phase Microscopy with Molecular Vibrational Sensitivity

摘要： Quantitative phase imaging (QPI) has become a valuable tool for studying optically transparent samples such as biological cells and tissues. It yields the sample-specific optical path-length delay at each spatial point of the field of view with a nanometer resolution, enabling high-contrast and objective analysis. The major advantage of QPI is its wide-field, label-free measurement capability of the transparent morphology. This allows for high-speed imaging limited by the image sensor’s frame rate while reducing optical and/or chemical damages to the sample which are troublesome in other imaging techniques such as fluorescence and Raman imaging. To date, QPI has been used for pathology diagnosis, phenotyping of live cancer cells, non-destructive measurement of cellular volume and dry-mass, study of cellular membrane dynamics, to just name a few. However, QPI lacks chemical sensitivity which limits its application to morphology-based diagnosis. Here, we report on our wide-field label-free molecular-vibrational (MV) microscopy method realized in the framework of QPI utilizing mid-infrared (MIR) photothermal effect. We measure local changes in the optical phase delay occurring upon absorption of the MIR light in the vicinity of the MV-resonant molecules, which is called photothermal effect, by means of QPI. This imaging scheme yields high-molecular-detection sensitivity based on MV-resonant MIR absorption having ~8 orders of magnitude larger cross-section compared to Raman scattering. Meanwhile, it also maintains the visible-light spatial resolution, high temporal resolution limited by the image sensor’s frame rate, and low photodamage to the sample with the wide-field, low-fluence optical illumination. Notably, our wide-field, parallelized detection scheme could even surpass the imaging speed of conventional label-free imaging methods such as coherent Raman imaging by an order of magnitude, as they typically employ a point-scanning mechanism for image synthesis. Our MV-sensitive QPI (MV-QPI) could offer new insights for optically-transparent complex dynamics by enabling high-speed, label-free cross-correlative analysis based on the quantitative morphology and the MV-spectroscopic chemical contrasts.