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Connecting two worlds:high-tech microscopy resolves“impossible” questions

by Nicole Testerink

Please check full issue of ICMS Highlights magazine here.

Yuyang Wangʼs door is always open. As Facility Manager of ICMSʼs Advanced Microscopy Facility, he is eager to help researchers further their research. When postdoc Hailin Fu is challenged in studying her new structures with the microscope techniques previously available, Wang develops a new microscope setting himself. Thanks to Wangʼs efforts, they manage to perform orientationbased research with polarization microscopy for the very first time. Their joint research leads to an exciting paper in the renowned journal Nature.

ICMS tries to facilitate its researchers in various ways, for example by clustering expertise. Like at the Advanced Microscopy Facility. Facility manager Yuyang Wang has several state-of-the-art microscopes under his care. “Within ICMS, we do a lot of research at the micro- and nanoscale. Therefore, many microscopes are already present within the various research groups. Researchers try to answer their research questions using the microscopes that are available in their labs. But within the Advanced Microscopy Facility, we look one step ahead. We do not stop when things seem impossible. In those cases, we offer high-level support by developing custom microscopy.”

And so is the research question Hailin Fu is struggling with. In a supramolecular polymer solution that she leaves overnight, she discovers that some structures segregate and form small islands. Using various fluorescent labels and microscopic methods, she tries to characterize the structures called tactoids, but fails to make statements about the orientation of fibrils inside. Wang sees it as a challenge. “We like to make the impossible possible. With conventional confocal microscopy, Fu could follow tactoid formation very nicely in the best resolution one can acquire using such microscopy method. But she also wanted to see how the fibrils were oriented inside these structures, at a higher resolution. Polarization microscopy enables such study of orientation.” (see box)

But the technique needs to be adjusted for the visualization of the fibrils inside the tactoids, Wang explains. “As a microscopist, I use a lot of organic dyes for the labeling of different things. But these dyes are rigid molecules that emit light in a certain direction. They attach to the desired molecule in a random fashion. In this case, since we would like to investigate the specific orientation of the fibrils, we had to eliminate this randomness.” Therefore, they use a different dye, developed in the research labs of Bert Meijer and Patricia Dankers. Wang quickly draws out the structure on a paper and points to a specific piece. “This is where the magic happens. The short linker within the dye results in less flexibility. In this way, it could indeed reflect the internal geometry of the fibrils inside the tactoids.”


Using the polarization microscopy setting that Wang develops and builds, Fu can finally visualize that the fibrils are highly orderly structured. The start of a whole series of experiments, stresses Wang. “Fuʼs results are chemically very exciting. But the microscopic technology we developed for this is also very unique. High-tech microscopy techniques are predominantly developed in the biological field. We are pushing the boundaries of material microscopy, thereby bridging the gap. We are the only material based super resolution center in the region, giving us a unique position.”


“Fuʼs research is a good example on how microscopy can help make the seemingly impossible possible. And the developments do not stop with this paper, because we would also like to visualize tactoid dynamics in even higher detail. Furthermore, TU/e-researchers in several departments are trying to connect live cell imaging and electron microscopy. We are also collaborating with companies such as Thermo Fisher Scientific (Brainport Eindhoven), that designs hardware and software to enable this.” “Another exciting development is the reorganization of several ICMS labs to create a modular prototyping platform for advanced microscopy. By investing in new infrastructure, new techniques, and high throughput sampling we aim to bring fundamental research from the lab to the industry.” Wang smiles. “Also in this area the interactions are highly dynamic.”


Within the Advanced Microscopy Center, Wang is now busy expanding the microscopic support, he tells enthusiastically. “We want to make it even clearer to researchers that we are here for them, and want to contribute ideas on how (super-resolution) microscopy can help with their research questions. We therefore have new ways to promote our facility. A new logo, a new website (see box) to better communicate our expertise and other possibilities.”

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