A microscope for fast and super-resolution fluorescence imaging

Fluorescence microscopy is an indispensable tool in biological sciences. Over the years, the need for faster imaging systems increased with the growing number of three-dimensional samples. The goal of this project is the construction of a fast and sensitive line-scan confocal microscope. The proposed instrument will acquire images at least an order of magnitude faster than point-scan confocal microscopes without compromising sensitivity. The fast scanning speed and sensitive detection will allow for in-tissue single-molecule localization imaging. The unique design of the microscope with minimal optical elements will deliver a robust and modular system. The imaging performance will be enhanced by the addition of PSF-engineering to improve single-molecule imaging. After building the instrument, the performance will be showcased on imaging of spatially resolved transcriptomics of breast cancer tissues in collaboration with Prof. Thierry Voet. Developing an automatized imaging system for MERFISH analysis with this microscope will cut down on total imaging time drastically and improve the detection sensitivity. To illustrate the potential and importance of single-molecule imaging in thicker samples, vesicle trafficking on hippocampal brain slices will be investigated with Dr. Lydia Danglot.