High specificity quantitative phase imaging with scattering markers

Strategic Research Initiatives

Gabriel Popescu: Electrical and Computer Engineering

Hyunjoon Kong: Chemical and Biomolecular Engineering

Addressing the Problem

Fluorescent microscopy is an established imaging tool in cell biology due to its molecular level specificity. Unfortunately, exogenous fluorescent labeling induces drawbacks (i.e., photobleaching and phototoxicity) that prevents this technique for long-term and quantitative investigation. On the other hand, quantitative phase imaging is an emerging label-free microscopic technique. By measuring the light scattered by the specimen, QPI measure cell morphology and dynamics with extreme high sensitivity. However, in the absence labels, QPI cannot identify particular sub-cellular structures with high specificity. Since QPI signals relies on refractive index contrast between the cell and background, it might be possible to enhance imaging specificity by labeling structures of interest with highly scattering markers

Research Goals

The goal of this research is to develop high refractive index nanoparticles, named Zeolitic imidazolate frameworks (ZIF), to enhance imaging specificity in quantitative phase imaging. Encapsulated organelle specific proteins, we expect these nanoparticles enter, migrate and eventually combine with the targeted structure. Measured by spatial light interference microscopy (SLIM), we expect the QPI signal from the region with nanoparticles can be greatly enhanced, and the labeled organelles can be easily identified.