Biomedical researchers develop and use organoids as a tool to study human development and disease. These small, laboratory-grown cultures mimic human organs and provide a keen overview of tissue development, drug interactions and other biochemical functions, offering an innovative approach to personalized medicine.
“Getting detailed 3D images of these miniature models of organs and getting a good look at how they change under different conditions or stimuli can tell us a lot about how the body works,” said Shuichi Takayama, professor and Price Gilbert Jr. Chair in Regenerative Engineering and Medicine in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. “It can tell us how diseases progress or how mechanical forces and certain drugs can change or affect cell behavior.”
The trick is to get these detailed images. 3D fluorescence microscopy has helped transform the study of organoids at the cellular and subcellular levels, albeit with some drawbacks. Conventional methods are time-consuming and do not adequately capture the fast, dynamic, sometimes unpredictable cell and tissue processes of these model systems.
Now a team of Georgia Tech researchers has developed a better system to quickly create high-resolution, real-time 3D images that enable quantitative analysis of organoids. Led by Coulter BME Assistant Professor Shu Jia, their custom-built microscope can reconstruct a comprehensive 3D representation using a single camera image. They described their system in the magazine biosensors and bioelectronics.
Jia’s new system builds on his lab’s growing body of work on next-generation imaging systems. Traditional 3D imaging technologies rely on time-consuming, redundant scan-based techniques that can result in damaged cells and compromised images. Jia’s team has developed a faster light field system that offers higher resolution and minimizes photo damage. Your new system does all that and more.
“This latest system is novel because it is fully tailored for tissue- and animal-scale imaging,” said Jia, who received a CAREER award from the National Science Foundation earlier this year. “We built everything from scratch on an optical table.”
The addition of a hybrid point-spread capability to the new system allows researchers to capture scan-free images of intact organoids in all their dynamic glory in milliseconds instead of minutes or even hours using traditional methods. With a single camera image, Jia’s system can reconstruct a time-lapse observation of the 3D volume of the samples.
“We can view – cell by cell – the entire organoid in high spatial and temporal resolution and see from multiple vantage points what is happening as a result of an external perturbation or a response to a specific drug or a change in the overall environment,” Jia said.
He said the imaging systems from his lab have the potential to transform traditional 3D microscopy.
“Because it’s a custom system, it’s very flexible and adaptable,” he added. “It works with organoids, but it can also work with animal models. I think we can extend this method to different research areas. There are a number of potential collaborations that we are evaluating.”
This research was supported by the National Institutes of Health (Grant Nos. R35GM124846 and AI116482) and the National Science Foundation (Grant Nos. EFMA1830941 and 2145235). All opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of any funding body.