Development of the next generation of microscopes

Development of the next generation of microscopes

image: : Florian Ströhl originally had the idea a few years ago. “I built the very first prototype by hand. It took forever as I had to do everything manually. So I was very relieved when it delivered results and great images,” says Ströhl.
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Photo credit: Kjetil Rydland/UiT

To observe living cells through a microscope, a sample is usually pressed onto a glass slide. It then lies quietly and the cells can be observed. The disadvantage is that this limits the behavior of the cells and only produces two-dimensional images.

Researchers from UiT The Arctic University of Norway and the University Hospital of North Norway (UNN) have now developed the next-generation microscope. The new technology can take pictures of much larger samples than before while living and working in a more natural environment.

The technology provides 3D images in which researchers can clearly and visually examine the smallest details from multiple angles, sorted into different slices and all slices in focus.

3D microscopes already exist, but they work slowly and produce inferior results. The most common way works by serially capturing pixel by pixel, which is then assembled into a 3D image. This takes time and often they can’t do more than 1-5 shots per minute. It’s not very practical when you want to photograph something that’s moving.

“With our technology, we create around 100 full frames per second. And we believe that it is possible to increase this number. That’s exactly what we demonstrated with our prototype,” says Florian Ströhl, researcher at the UiT.

The new microscope is a so-called multi-focus microscope, which provides completely clear images, sorted into different layers, where you can examine the cells from all angles.

“It’s big business. Being able to do it all in one take is a huge development,” says Ströhl.

Ströhl explains that we are not talking about 3D in the way most of us are familiar with it.
While you can see some depth in a traditional 3D image, the new technology also allows you to see behind objects.

Ströhl uses an example where you see a jungle scene in 3D in the cinema.

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

Now you don’t use a microscope to look for tigers in the jungle, but for researchers it can be an important tool when it comes to searching for answers down to the smallest detail.

Ströhl worked with researchers and doctors at the University Hospital of Northern Norway (UNN) to develop this technology.

Among other things, they work to understand and develop better treatment methods for various heart diseases.

Studying a living human heart is challenging, both for technical and, last but not least, for ethical reasons. So researchers have used stem cells engineered to mimic heart cells.
This allows them to grow organic tissue that behaves like a human heart, and they can study and test that tissue to understand more about what’s happening.

This tissue is almost like a small lump of living flesh, about 1 cm in size. This leads to a very demanding testing situation where heart cells are beating and constantly moving along because the sample is too big to examine with traditional microscopes.
The new microscope copes well with it.

“You have this pumping lump of meat in a bowl that you want to take microscope pictures of. You want to see the tiniest bits of it, and you want super high resolution. We managed to do that with the new microscope,” says Ströhl.

Kenneth Bowitz Larsen runs a large laboratory with advanced microscopes used by all research groups in UiT’s Faculty of Health.
He has tested this new microscope and is optimistic.

“The concept is brilliant, the microscope they built does things that commercial systems can’t do,” explains Larsen.
The laboratory he runs mainly uses commercially available microscopes from manufacturers such as Zeiss, Nikon, etc.

“Then we also work together with research groups like those represented by Florian Ströhl. They build microscopes and test optical concepts, they are something like the Formula 1 division of microscopy,” says Larsen.
Larsen has great confidence in the new microscope that Ströhl has developed.

The commercial microscopes have to be usable for all kinds of samples, while the microscope developed by Ströhl is more tailored to a specific task.

“It is very sensitive to light and can display the sample in different focuses. It can work its way through the sample and you can see both high and low. And so fast that you can see it practically in real time. It’s an extremely fast microscope,” says Larsen.

According to Larsen, tests so far show that this works well, and he believes this type of microscope can ultimately be used for all types of samples where you’re looking at living things that move.

He sees another advantage in the speed of this microscope.

“Bright light is not good for cells. Because this microscope is so fast, it exposes the cells for a much shorter time and is therefore gentler,” he explains.

The prototype of the microscope works and is ready for use. Researchers are currently working on an improved version that is easier to use so that more people can operate and use the microscope.

The researchers have also applied for a patent and are also looking for industrial partners who can use it to develop a commercially available microscope.

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 challenging samples that they want to have examined,” says Ströhl.


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