Super-resolution molecular imaging allows close look at organoid development

Chao Zhou’s lab to use new method that takes a combined approach

Beth Miller 
Chao Zhou

Because conventional microscopes are limited in resolution, researchers have begun using a technique called expansion microscopy that introduces a chemical process to expand the samples for a closer look with the same equipment. 

Chao Zhou, associate professor of biomedical engineering in the McKelvey School of Engineering, plans to develop expansion optical coherence microscopy (ExOCM), a super-resolution imaging method that will provide multi-color imaging of organoids, which are 3D organ-like tissue cultures derived from stem cells. He and his team will look at the organoids over time while they are developing, then expand them to see finer detail.

With a two-year, $430,834 grant from the National Institutes of Health, Zhou and his lab will develop and validate the technology and demonstrate its usefulness in developmental biology, cancer research and regenerative medicine.

“Compared with standard expansion microscopy, ExOCM can image extra-thick samples at high speed,” Zhou said. “We will build on our group’s expertise with 3D microscopy to show the unique attributes of ExOCM for biomedical research.”

Zhou’s lab developed optical coherence tomography (OCT), a fast, safe and noninvasive imaging method that detects differences in how tissue refracts light and can acquire high-resolution 3D images with a depth of up to 1 to 2 millimeters in less than a minute. Earlier this year, he and his team published work that used OCT to see human heart organoids beating and developing over time. Now, he and his team will combine OCT with expansion microscopy to obtain up to a 300-nanometer resolution in images.

Using OCT, the team will acquire images of living organoids over a three-week period. These 3D time-lapse images will provide a look into the development process of the organoids. At several points during the three weeks, they will take samples from the organoids and expand them for ExOCM.

“We will obtain 3D structural and molecular profiles of the samples using ExOCM, then correlate those profiles with growth dynamics measured from live samples using OCT, which shows the unique advantages of the combined OCT and ExOCM imaging technique,” Zhou said. “Then, 3D molecular profiles, such as distribution of different cell types, can be mapped out with high resolution.” 

The ExOCM data collected during the expansion process will give the team first-hand information about 3D expansion uniformity.

“If successful, this technology would allow molecular-specific, super-resolution imaging of 3D samples with high imaging speed,” Zhou said. “Combined with label-free OCT images obtained from the same platform, the proposed system can be used to accurately register changes in 3D tissue microstructure obtained from living samples with multiplexed 3D molecular information from the same sample.”

The images also can be acquired using commercially available OCT systems, making the technique available to a broader research community.

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