MRI: Development of a hybrid quantitative phase microscope for live cell imaging

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1039562WaxThe goal of this research is to develop a novel quantitative phase microscope for investigating and analyzing changes in cellular structure and function due to environmental influences and pathology due to disease. To achieve this goal, a hybrid optical interferometric imaging and sensing system is proposed, combining low-coherence wide-field digital interferometry (WFDI), capable of visualizing fast cellular dynamics, with a novel optical coherence tomography (OCT) approach that uses photothermal heating of plasmonic nanoparticles (NPs) to achieve molecular imaging. The role of the low-coherence WFDI system is to visualize cell dynamics in order to assess modulation of cell function due to external influences. This transmission-mode system will quantitatively record optical path delays of light that has been transmitted through the sample, and thus will create quantitative phase images of local refractive index changes. This information can be used to characterize dynamic cell phenomena, as well as to account for transport of intracellular materials, which can characterize various types of disease. The OCT system will be used to detect molecular species such as cell surface receptors and the location and density of intracellular proteins. Gold NPs, functionalized to bind to specific molecules, will be heated selectively using the photothermal method, with excitation tuned to the NP plasmon resonance wavelength, to enable molecularly selective sensing by OCT. The hybrid system is expected to allow a wide range of studies of cellular dynamics, while the combination of the two sub-systems (WFDI and OCT) will enable investigation of modulation of dynamic behaviors due to onset and progression of disease.