Research Experiences

Washington University in St. Louis

Single-Molecule Orientation Localization Microscopy (SMOLM): Fundamental Limits, Computational Methods, and Biological Imaging Applications

May 2022 - present， Advisor: Dr. Matthew D. Lew

• Theoretical Modeling & Analysis
  • Discovered fundamental degeneracies and precision limits for distinguishing pairs of spatially overlapping dipole emitters from rotating single molecules, and derived the mathematical necessity of measuring fourth-order orientation moments.
  • Developed combined excitation-polarization and emission dipole-spread-function (DSF) modulation strategies, improving angular-separation measurement precision by 200-400% and centroid-orientation precision by 50% over state-of-the-art methods.
  • Investigating fourth-order-moment measurement strategies to expand the accessible parameter space for resolving higher-order orientational dynamics.
    
• Computational Imaging & Algorithm Development
  • Engineered DSFs by maximizing Fisher information using convex optimization approaches tailored to targeted orientation regimes.
  • Designed a physics-informed SMOLM data-generation pipeline for high-fidelity DeepSMOLM3D training and validation datasets, enabling accurate modeling of complex 6D imaging parameters.
  • Conducted comprehensive simulation studies across signal-to-noise ratio, molecular density, and other imaging conditions, as well as experimental trials on cell membrane imaging, demonstrating improved accuracy, precision, and reconstruction speed compared with traditional maximum-likelihood estimation under challenging imaging scenarios.
• Optical Systems & Biophysical Applications
  • Executed full optical alignment and calibration of a dual-polarization 4f imaging system incorporating a liquid-crystal spatial light modulator (SLM) for precise phase modulation.
  • Performed PAINT single-molecule imaging of supported lipid bilayers (SLBs) and cell membranes using membrane-sensitive fluorogenic fluorophores, revealing fluorophore-dependent binding dynamics on membrane structures.
  • Optimizing protein-tag-based labeling strategies for robust measurements of cell membrane orientation and rotational dynamics.

Nankai University

Study of Human Red Blood Cell (hRBC) Membrane Characteristics Based on Microfluidics and Single-Molecule Localization Microscopy

April 2019 - June 2021, Advisor: Dr. Leiting Pan

• Quantified hRBC deformability by measuring cell transport speeds through narrow microfluidic channels.
• Designed and simulated a novel microfluidic ratchet chip using COMSOL Multiphysics to sort hRBCs based on age-related deformability.
• Analyzed the hRBC actin-spectrin network and CD47 diffusivity on hRBC membranes using single-molecule localization microscopy (SMLM).