BIOE 500 Spring 2026 - Graduate Student Minsung Kwon

Developing label-free biochemical imaging using quantitative phase imaging and mid-infrared photothermal effects

Abstract: Quantitative phase imaging (QPI) has been widely recognized for its ability to provide high-contrast, label-free images. Spatial light interference microscopy (SLIM), based on common-path interferometry, offers exceptional phase stability. However, the system response, particularly the relationship between illumination geometry and image contrast, has not been thoroughly studied. Under the weak scattering approximation and within the transmission cross-coefficient (TCC) framework, spatial contrast can be tuned to specific feature sizes, providing a valuable tool to optimize quantitative phase measurements in biological samples. Furthermore, a conventional Zernike phase contrast microscope was modified to enable single-snapshot phase measurement via polarization multiplexing. Four phase-shifted interferograms can be captured simultaneously in different polarization channels, eliminating sequential measurements. This enhancement improves temporal resolution (up to 100 fps), reducing motion artifacts and enabling the extraction of dynamic contrast, which revealed organelle-specific features in live neurons through temporal spectral analysis. To expand the system’s capabilities, mid-infrared photothermal effects will be integrated, providing bond-specific hyperspectral contrast. This approach overcomes QPI’s fundamental limitation—lack of molecular specificity—without the need for extraneous labels. By combining high-resolution, dynamic, and molecular-specific imaging, this work aims to advance the quantitative understanding of biomechanical processes through multidimensional contrast.

By Minsung Kwon, Beckman Institute for Advanced Science and Technology, Faculty Advisor, Rohit Bhargava