Overcoming the fundamental limitation of frequency-domain fluorescence lifetime imaging microscopy spatial resolution

Abstract

We propose and demonstrate the first analytical model of the spatial resolution of frequency-domain (FD) fluorescence lifetime imaging microscopy (FLIM) that explains how it is fundamentally different with the common resolution limit of the conventional fluorescence microscopy. Frequency modulation (FM) capture effect is also observed by the model, which results in distorted FLIM measurements. A super-resolution FLIM approach based on a localization-based technique, super-resolution radial fluctuations (SRRF), is presented. In this approach, we separately process the intensity and lifetime to generate a super-resolution FLIM composite image. The capability of the approach is validated both numerically and experimentally in fixed cells sample.

Publication
SPIE Photonics West 2021, Online Only
Yide Zhang
Yide Zhang
NIH K99 Postdoctoral Fellow

My research is interdisciplinary and focused on developing new types of optical imaging techniques that could advance the work of other researchers and medical personnel in a wide variety of fields. Currently, I am developing next-generation photoacoustic and ultrafast imaging techniques that can observe biological and physical phenomena that are too fast to be imaged with existing methods. The observation of the ultrafast phenomena could provide a better understanding of the fundamentals of life and physical sciences. I am also developing novel quantum imaging approaches that can investigate biological organisms with an imaging performance that cannot be achieved using classical optical imaging. In my free time, I enjoy cooking, hiking, cycling, and traveling.

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