Interferometric Microscopy and Nanoscopy in Live Biological Cells and Tissues

Final Report Summary - IMANILBCAT (Interferometric Microscopy and Nanoscopy in Live Biological Cells and Tissues)

This project suggested new interferometric methods that can be used for live cell quantitative measurements with sub-nanometer accuracy. Being able to perform nano-sensing of cell thicknesses using optical interferometry opens new horizons for biomedical applications. My research aimed at solving several critical technological problems left in the field and using these methods for new biomedical applications. In this project, we had three objectives: (1) Novel optical-mechanical signatures of cancer cells measured by interferometry; (2) Interferometric diagnosis of red blood cells; and (3) Developing plasmonic nanoparticle-based interferometric methods for neurons. We had great advances in each of these objectives, and each direction yielded several publications. We first proposed a compact off-axis interferometric module that solves critical problems in conventional interferometric setups, such as their bulkiness and hard alignment, but is still able to obtain high-accuracy optical thickness profiles of live cells. Then, we used this portable interferometric technique for measuring live cancer cells, and showed that the cell optical thickness profile fluctuates more in cancer cells compared to healthy cells, as well as fluctuates more in metastatic cancer cells compared to primary cancer cells, a technique that has the potential for cancer grading. We also proposed a different compact interferometric system that can monitor dynamic processes, such as drug delivery in vitro, in high temporal resolution, much faster than it has been possible till now. In addition, we have proposed novel methods to double or triple the interferometric field of view or the camera frame rate, without resolution or magnification loss, which enables fast dynamic acquisition, and helps in imaging of microchannels and neuronal dynamics. To enable clinical use of these methods, we presented new algorithms that enable real-time processing of the off-axis interferograms to the optical thickness profiles. This was the first time that more than video-rate processing could be obtained using a simple single-core computer. Demonstrations were given for red blood cells in a microchannel. We have also presented a photothermal imaging method that is based on labelling with plasmonic nanoparticles excited optically, which adds molecular specificity to interferometry. These published works also included new numerical model that allows calculating the shape of the best plasmonic nanoparticle for photothermal phase imaging. Finally, tomographic phase microscopy results for 3-D refractive-index imaging using a unique method of single cell rotation were also obtained, by collaborating with German group.

The support of the grant helped me tremendously. It allowed me to requite good students, allowed me travels to collaborators and conferences, in which I presented the CIG research to the research community of my field, and allowed me to publish in the best peer-review journals of my field, including two papers in Nature LSA. The initial results obtained under the CIG also helped me obtaining the prestigious support of the Horizon2020 ERC starter grant, which starts soon, 3 months after the end of the CIG period. These results and publications also allowed me to obtain the position of a Tenured Associate Professor in my university, right at the end of the period of the CIG.

My group website: www.eng.tau.ac.il/~omni. All papers published can be downloaded from this website.