Abstract:

Advancing the frontiers of biomedical imaging requires platforms that can deliver high-resolution, high-speed, and stable volumetric imaging across diverse biological scales. This dissertation presents three complementary innovations in optical microscopy that collectively address the limitations of traditional light-sheet and oblique plane imaging systems in terms of complexity, drift, resolution, and imaging throughput.

First, we introduce Reflected Inline Detection in Epi-Oblique Plane Microscopy (RIDE-OPM)—a compact, drift-resistant imaging system that eliminates the need for complex detection path. By leveraging the full numerical aperture of standard objectives without sacrificing alignment or tilt flexibility, RIDE-OPM simplifies system architecture and enables robust long-term imaging of live samples with minimal photodamage. Second, we describe a high-speed Axially Swept Light-Sheet Microscopy (ASLM) platform designed for large, optically cleared tissues. This system utilizes dual fixed light-sheet foci and synchronized sweeping to achieve isotropic sub-micron resolution at up to 40 frames per second—a four-fold improvement over conventional ASLM. Integrated with a deep learning–based tissue boundary detector, the platform supports rapid and high-contrast 3D imaging across various clearing protocols. Finally, we propose a customizable remote focusing architecture that enables precise multi-scale imaging by aligning multiple primary objectives with a single remote objective using identical optical elements. This solution ensures consistent 4f geometry and magnification matching, providing a flexible and effective alternative for systems requiring frequent objective switching.Together, these three innovations establish a cohesive framework for next-generation microscopy that overcomes mechanical instability, enhances optical performance, and improves usability for live, cleared, and multi-resolution imaging applications.

Biography:

Md Nasful Huda Prince started his Ph.D. in Optical Science and Engineering with a focus in Imaging Science at the University of New Mexico, where he is part of Dr. Tonmoy Chakraborty’s research group. His doctoral research involves the development of advanced light-sheet imaging modalities. During his doctoral work, he successfully designed and built three distinct imaging platforms based on: axially swept light-sheet, oblique plane microscopy, and lattice light-sheet. He also earned a Master’s degree in Optical Science from UNM en route to his Ph.D.

Prince holds a Bachelor’s degree in Electrical and Electronic Engineering (EEE) from Khulna University of Engineering and Technology, an MBA in Finance from Jahangirnagar University, and a Master’s degree in EEE from Bangladesh University of Engineering and Technology (BUET). Besides his academic studies, he served in key technical roles within Bangladesh’s national telecommunications and power transmission industry.