Research Experiences

Washington University in St. Louis

Seeing Molecular Orientation in Six Dimensions

My doctoral research asks how much we can learn about the orientations and rotational dynamics of individual molecules from the light they emit. I focus on single-molecule orientation-localization microscopy (SMOLM), combining theoretical modeling, optical engineering, and computational imaging to measure molecular position and orientation at the nanoscale.

One central challenge is distinguishing two molecules whose images spatially overlap. I discovered fundamental degeneracies that limit this measurement and showed mathematically that resolving certain orientational differences requires access to fourth-order orientation moments. Building on this result, I developed an imaging strategy that combines excitation-polarization modulation with engineered dipole-spread functions. Simulations showed that this approach improves angular-separation precision by 200-400% and centroid-orientation precision by approximately 50% compared with existing methods.

I also develop computational tools that translate these theoretical insights into practical imaging methods. This work includes optimizing dipole-spread functions using Fisher information and convex optimization, as well as building a physics-informed data-generation pipeline for training DeepSMOLM3D. Through simulations and cell-membrane experiments, I have evaluated these methods across varying molecular densities, signal levels, and imaging conditions.

Experimentally, I built and calibrated a dual-polarization 4f microscope with spatial-light-modulator-based phase control. I use this system to study supported lipid bilayers and cell membranes with fluorogenic probes, investigating how probe chemistry and labeling strategies influence measured binding and rotational dynamics. My current work explores fourth-order-moment measurements and protein-tag-based labeling for more robust characterization of membrane organization.

Nankai University

Connecting Red Blood Cell Mechanics and Membrane Organization

My undergraduate research examined how the mechanical properties of human red blood cells relate to their membrane organization. I first used microfluidic channels to measure cell deformability through transport speed. I then designed and simulated a microfluidic ratchet device in COMSOL Multiphysics to explore whether cells could be sorted according to age-related differences in deformability.

To examine the membrane at a smaller scale, I used single-molecule localization microscopy to study the actin-spectrin network and the diffusion of CD47. This experience introduced me to the connection between physical measurement, optical imaging, and biological function, which continues to shape my current research.