Research Summary

My research is interdisciplinary and focused on developing new types of fluorescence microscopes that could advance the work of other researchers and medical personnel in a wide variety of fields. My research interests include multiphoton microscopy (MPM), fluorescence lifetime imaging microscopy (FLIM), super-resolution microscopy, high-speed imaging, deep tissue imaging, adaptive optics, computational imaging, and deep learning. In general, I design and build novel fluorescence microscopes with improved imaging speed, resolution, depth, and functionality over conventional microscopes.

  • Speed
    • Super-Sensitivity MPM-FLIM
    • Saturation-Compensated FLIM
    • Phase-Multiplexing FLIM
  • Resolution
    • Super-Resolution: Stepwise Optical Saturation (SOS)
    • Super-Resolution: Deconvolution Stepwise Optical Saturation (DeSOS)
    • Super-Resolution FLIM: Generalized Stepwise Optical Saturation (GSOS)
  • Depth
    • Sensorless Adaptive Optics
    • Image Denoising by Deep Learning
  • Functionality
    • FLIM Phasor Plots
    • Automatic Image Segmentation by K-Means Clustering


Here is an example of the images I acquired using a custom-built phase-multiplexing MPM-FLIM:

Yide Zhang, Ian H. Guldner, Evan L. Nichols, David Benirschke, Cody J. Smith, Siyuan Zhang, and Scott S. Howard, “Three-dimensional deep tissue multiphoton frequency-domain fluorescence lifetime imaging microscopy via phase multiplexing and adaptive optics”, SPIE Photonics West 2019, San Francisco, California USA, Feb. 2019.


Here is a comparison between conventional and DeSOS microscopy images:

Yide Zhang, Evan L. Nichols, Abigail M. Zellmer, Ian H. Guldner, Cody Kankel, Siyuan Zhang, Scott S. Howard, and Cody J. Smith, “Generating intravital super-resolution movies with conventional microscopy reveals actin dynamics that construct pioneer axons”, Development, Feb. 2019, doi: 10.1242/dev.171512. Supplementary software available at doi: 10.7274/r0-5hhg-5578.