Microscope Captures High-Speed Images of Living Cells in 3D

A limitation to conventional microscopy imaging, in which a sample is usually squeezed onto a glass slide, is that the behavior of the cells may differ from their natural environment. Further, the the images obtained via this approach are two-dimensional.

To overcome these limitations together, researchers from UiT The Arctic University of Norway and the University Hospital of North Norway (UNN) developed a multifocus microscope to image larger samples in a more natural environment, as well as in 3D.

With the technology, according to Florian Ströhl, a researcher at UiT, the researchers managed around 100 fps with the device.

Although 3D microscopes already exist, their applications can be limited due to the slow speed at which they image. Typically, these devices can only take between one and five images per minute, limiting their utility for living and moving cells.

The prototype multifocus microscope developed at UiT takes clear images at different depths of focus that are sorted into layers. Courtesy of UiT.

The prototype is a multifocus microscope that provides clear images sorted into different layers. This is a different approach than traditional 3D imaging. Ströhl used the example of a 3D jungle scene in a movie.

“In a normal 3D image, you can see that the forest has a depth, that some leaves and trees are closer than others. With the same technology used in our new 3D microscope, you are also able to see the tiger hiding behind the bushes. You are able to see and study several layers independently,” he said.

The microscope was tested by Kenneth Bowitz Larsen, who heads a large laboratory featuring advanced microscopy systems used by research groups at the Faculty of Health at UiT.

“The concept is brilliant; the microscope they have built does things that the commercial systems do not,” Larsen said. The laboratory he heads mainly uses commercial microscopes from suppliers like Zeiss and Nikon.

The laboratory also collaborates with research groups such as the one Ströhl represents. “They build microscopes and test optical concepts; they are in a way like the Formula 1 division of microscopy,” Larsen said.

The commercial microscopes in Larsen’s lab need to be able to conduct a variety of tasks, though the microscope developed by Ströhl’s team is tailored to more specific tasks.

“It is very photosensitive, and it can depict the specimen in various focuses. It can work its way through the sample and you can view both high and low. And it happens so fast that it can practically be seen in real time. It's an extremely fast microscope,” Larsen said.

A team used the microscope to study heart tissue; researchers at UNN use stem cells that are manipulated to mimic heart cells. In this way, they can grow organic tissue that behaves as it would in a human heart. The tissue sample is about 1 cm, making it too large to image with ordinary microscopy methods, with the additional challenge of the cells being in constant motion.

“You have this pumping lump of meat in a bowl, which you want to take microscope pictures of. You want to view at the very smallest parts of this, and you want superhigh resolution. We have achieved this with the new microscope,” Ströhl said.

The speed of the microscope is not only a boon for imaging cells in motion, but it also limits photodamage.

“Bright lights are not kind to cells. Since this microscope is so fast, it exposes the cells to much shorter illumination and is therefore more gentle,” Larsen explained.

The team applied for a patent and is looking for industrial partners to develop the microscope into a commercial product. To that end, the team is working to develop an upgraded version to make it easier to use for a broader audience. In the meantime, the prototype will be made available to local partners who can benefit from the new technology.

“We will also offer it to others in Norway, if they have particularly demanding samples that they want examined,” Ströhl said.

The research was published in Optica (www.doi.org/10.1364/OPTICA.468583).