Optical nanoscopy has given a glimpse of the impact it may have on medical care in the future. Slow imaging speed and the complexity of the current nanoscope limits its use for living cells. The imaging speed is limited by the bulk optics that is used in present nanoscopy. In this project, I propose a paradigm-shift in the field of advanced microscopy by developing optical nanoscopy based on a photonic integrated circuit. The project will take advantage of nanotechnology to fabricate an advance waveguide-chip, while fast telecom optical devices will provide switching of light to the chip, enhancing the speed of imaging. This unconventional route will change the field of optical microscopy, as a simple chip-based system can be added to a normal microscope. In this project, I will build a waveguide-based structured-illumination microscope (W-SIM) to acquire fast images (25 Hz or better) from a living cell with an optical resolution of 50-100 nm. I will use W-SIM to discover the dynamics (opening and closing) of fenestrations (100 nm) present in the membrane of a living liver sinusoidal scavenger endothelial cell. It is believed among the Hepatology community that these fenestrations open and close dynamically, however there is no scientific evidence to support this hypothesis because of the lack of suitable tools. The successful imaging of fenestration kinetics in a live cell during this project will provide new fundamental knowledge and benefit human health with improved diagnoses and drug discovery for liver. Chip-based nanoscopy is a new research field, inherently making this a high-risk project, but the possible gains are also high. The W-SIM will be the first of its kind, which may open a new era of simple, integrated nanoscopy. The proposed multiple-disciplinary project requires a near-unique expertise in the field of laser physics, integrated optics, advanced microscopy and cell-biology that I have acquired at leading research centers on three continents.
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