Chromatin is a complex comprising of DNA and nuclear proteins and DNA that is densely packed within the cell nucleus. The organization and dynamics of chromatin play a crucial role in various nuclear activities, and disruptions in chromatin regulation are often associated with disease. Although the significance of chromatin in nuclear functions has been well recognized, characterizing the organization of chromatin at the nanoscale remains challenging, especially in the live cell nuclei.

To address this challenge, we are utilizing advanced label-free optical microscope techniques to investigate chromatin dynamics in live cells. Our highly sensitive interference microscopy allows us to directly measure the scattering light of unlabeled chromatin at high speed (>1000 fps). By analyzing the dynamic scattering images, we can extract the chromatin-specific temporal signal and reconstruct a high-resolution map of chromatin condensation states across the entire nucleus. This method is both non-invasive and quantitative, enabling accurate long-term measurements of chromatin structures and dynamics in live cells.