Keyi Han
BME PhD Proposal Presentation

Date: 2025-11-19
Time: Wednesday, November 19, 2025, 10:00AM – 11:30AM
Location / Meeting Link: Klaus 3100 Conference Room, https://gatech.zoom.us/j/2076572993

Committee Members:
Shu Jia, PhD (advisor); Francisco E Robles, PhD; Ahmet F Coskun, PhD; Sara Fridovich-Keil, PhD; Jeffrey E Markowitz, PhD;


Title: Towards Super-resolution Quanta Biophotonics

Abstract:
Over the past two decades, super-resolution microscopy (SRM) has overcome the diffraction limit of classical optical imaging, enabling visualization of subcellular structures with unprecedented clarity. Current SRM approaches rely on diverse physical and computational mechanisms. For instance, stimulated emission depletion microscopy manipulates molecular excited states, structured illumination microscopy recovers high spatial frequencies through patterned illumination, and single-molecule localization microscopy achieves nanometer precision through stochastic fluorophore activation. Additionally, statistical fluctuation analysis has emerged as a powerful route to extract super-resolved information from intrinsic fluorescence dynamics. While these techniques push the boundaries of illumination and fluorophore engineering, advances in detector technology remain comparatively underexplored. Single-photon avalanche diode–based quanta image sensors (SPAD-QIS) represent a transformative shift in imaging detection. Compared to conventional CMOS image sensors, SPAD-QIS offers single-photon sensitivity and binary output (quanta) at up to 100,000 frames per second. These detector capabilities open new opportunities for photon-efficient super-resolution imaging, but their full exploitation within the field is still emerging. This proposal aims to leverage SPAD-based quanta detection to advance super-resolution imaging microscopy. Aim 1 will develop a spatiotemporal super-resolution platform that integrates quanta detection with optical fluctuation analysis, and will extend this system through synergistic SPAD–sCMOS multiplexed imaging for single-cell studies. Aim 2 will establish a volumetric antibunching super-resolution microscopy by exploiting photon statistics in combination with light-field imaging to achieve 3D quantum-enhanced reconstruction. By bridging next-generation sensor technology with advanced SRM, this work will deliver powerful new imaging tools for probing biological processes and organizations across space and time.