Executive Summary : | Microscopy is a crucial tool in biological sciences, enabling the study of cell and tissue structure and behavior in unprecedented detail. However, light diffraction limits optical resolution in well-designed microscopes. Structured illumination microscopy (SIM) offers 100 nm resolution by illuminating with patterned light and analyzing the acquired images. However, image quality is degraded due to sensitivity to optical aberrations and sample drift. Adaptive optics (AO) is a powerful technique for correcting optical aberrations, bringing a 2-fold resolution increase. This project aims to design and build an AO-SIM that combines the two technologies. A computer model of SIM in Zemax OpticStudio will be created, including the patterned light source, objective and tube lenses, and other optical elements. A custom AO system will be integrated with a custom-designed SIM, including a high-intensity light source, a phase mask, and a camera. Custom software will be developed for control and synchronization of microscope hardware, light intensity, illumination pattern, and image acquisition software. Image registration software will be developed to reconstruct high-resolution images from multiple images captured with slightly different illumination angles or phases. AO-SIM will help visualize structures in living cells and tissues, enabling new discoveries in cellular biology, such as cellular signaling pathways, dynamics of cellular structures, and interactions between cells and their environment. Clinical applications include understanding disease progression, biomarker identification, targeted drug delivery, and diagnostic and therapeutic tools. This project is a crucial step towards translating AO-SIM, accelerating our understanding of complex processes in living organisms. |