To view living cells through a microscope, a sample is usually squeezed onto a glass slide. Then it lies there calmly and the cells are observable. The downside 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 what they call the next generation microscope. The new technology can take pictures of much larger specimens than before while living and working in a more natural environment.
An important development
The technology provides 3D images where researchers can study the smallest details from multiple angles, clearly and visibly, sorted into different layers, and all layers are in focus.
3D microscopes already exist, but they work slowly and give worse results. The most common type works by recording pixel by pixel in series, which are then assembled into a 3D image. This takes time and they often can’t handle more than 1-5 strokes per minute. It’s not very practical if what you’re about to photograph is something that moves.
“With our technology, we are able to handle around 100 full frames per second. And we believe it is possible to increase this number. This is precisely what we have demonstrated with our prototype,” says Florian Ströhl, researcher at UiT.
The new microscope is a so-called multifocus microscope, which provides completely clear images, arranged in several layers, where cells can be studied from all angles.
“It’s a big deal. The fact that we can achieve all of this in one take is a huge development,” says Ströhl.
Can see behind objects
Ströhl explains that we are not talking about 3D in the form that most of us know it. While in a traditional 3D image you will be able to perceive some sort of depth, with the new technology you will also be able to see behind objects.
Ströhl uses an example where you see a 3D jungle scene in the cinema.
“In a regular 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 are able to see and study different layers independently,” says Ströhl.
Now you don’t use a microscope to look for tigers in the jungle, but for researchers this can be an important tool when looking for answers in minute detail.
Study the cells of the heart as they beat
Ströhl collaborated with researchers and doctors from 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 reasons and not least for ethical reasons. Therefore, the researchers used stem cells manipulated to mimic heart cells. This way, they can grow organic tissue that behaves as it would in a human heart, and they can study and test this tissue to understand more about what’s going on.
This tissue is almost like a small piece of living flesh, about 1cm in size. This makes for a very challenging test situation, in which the heart cells are constantly beating and moving along it, making the sample too large to study with traditional microscopes. The new microscope handles that well.
“You have this pumping piece of meat in a bowl, that you want to take pictures of under a microscope. You want to see the smallest parts of this, and you want super high resolution. We did that with the new microscope,” Strohl says.
Formula 1 division
Kenneth Bowitz Larsen heads a large laboratory with advanced microscopes used by all research groups at the UIT Faculty of Health. He has tested this new microscope and is optimistic.
“The concept is brilliant, the microscope they’ve built does things that commercial systems don’t,” explains Larsen. The laboratory that he runs mainly uses commercial microscopes from suppliers such as Zeiss, Nikon, etc.
“Then we also cooperate with research groups like the one represented by Florian Ströhl. They build microscopes and test optical concepts, they are in a sense like the microscopy division of formula 1,” says Larsen. Larsen has great faith in the new microscope that Ströhl has created.
Commercial microscopes should be usable for all possible sample types, while the microscope developed by Ströhl is more suited to a specific task.
“It’s very light sensitive and can image the sample at various focal points. It can work its way through the sample and you can see both up and down. And it happens so fast that it can be seen in pretty much real time. It’s an extremely fast microscope,” says Larsen.
According to Larsen, the tests so far show that it works well, and he believes this type of microscope could eventually be used on all kinds of samples in which living things are observed moving.
He also sees another benefit with the speed of this microscope.
“Bright lights are not kind to cells. Because this microscope is so fast, it exposes cells to much shorter illumination and is therefore more delicate,” he explains.
The technology is patented
The microscope prototype works and is operational. The researchers are currently working on creating an updated version that is easier to use, so more people are able to operate and use the microscope.
The researchers have also applied for a patent and are also looking for industrial partners who will develop it into a microscope that will be available for sale.
In the meantime, the prototype will be made available to local partners who will be able to benefit from the new technology.
“We will also offer it to others in Norway, if they have particularly challenging samples they wish to examine,” says Ströhl.
The research was published in Optics.
Florian Ströhl et al, Multifocus Microscopy with Optical Sectioning and High Axial Resolution, Optics (2022). DOI: 10.1364/OTTICA.468583
Provided by UiT The Arctic University of Norway
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