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In the spinal cord of the zebrafish embryo, the new neurons glow in different colors, allowing scientists to track the development of the neural circuit Credit: T. Liu et al./Science 2018

Eric Betzig, who won the 2014 Nobel prize in chemistry, developed a super resolution fluorescence microscope and achieved a breakthrough. The team, led by him, has recently developed a microscope that combines 2 imaging techniques to enable researchers to observe the unprecedented 3D details of living cells, including cancer cell movement, spinal cord loop connections, and immune cells in the inner ear of zebrafish.

In April 20th, this result was published in Science magazine as “Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms”. The authors believe that the new technology solves the long-standing problem of cell imaging in living tissues and provides an exciting new perspective for biological research.

Overcoming obstacles to traditional microscopes

In order to obtain clear images, traditional microscopes usually isolate their experimental objects on a glass slide or irradiate them with potentially harmful harmful amounts of light. But Dr. Betzig thinks that observing the isolated cells on the slide is like going to the zoo to study the behavior of a lion (and do not see the true behavior of the cells in the original environment).
To overcome these hurdles, Dr Betzig and his team combined two microscopic techniques they first reported in 2014. Now, using this new device, researchers can observe them in the natural environment in which cells are located (rather than separate them, separate them out and observe them).

Imaging cellular diversity in a developing zebrafish

Two improvements in New Technology

The first step: let the cells “live”

In order to produce this immune cell video, Dr. Betzig and his colleagues avoided the strong light used by the traditional microscope because the light could destroy or kill living cells. Instead, the team used a technology called “lattice light-sheet microscopy”, which enables a thin layer of light (a thin sheet of light) to pass through living tissue at a very high speed, thereby reducing cell damage to a minimum level, and obtaining a series of 2D images and subcellular dynamics. High resolution 3D movies (building a high-resolution 3-D movie of subcellular dynamics).

The second step: to make the surrounding environment of cells not “distorted”.

At the same time, in order to make the surrounding environment of the cell not “distorted”, the researchers used adaptive optics (adaptive optics, an imaging technique used by astronomers). The technology can help solve the “distortion” problem and correct the image.

“Without adaptive optics, all these details are hard to see,” Dr. Betzig said. In his view, adaptive optics is one of the most important fields in the study of microscopes today, and the “lattice light sheet microscope”, which is good at 3D living body imaging, is the perfect platform for showing its strength. At the same time, he also pointed out that the current adaptive optics has not really “taken off”, because the technology is complex and expensive, but in the next 10 years, biologists around the world will be involved.

Unprecedented resolution of 3D

With the new microscope technology that combines “lattice light-sheet microscopy” and “adaptive optics”, researchers are now able to peek into the interior of organisms and observe intercellular interactions at an unprecedented 3D resolution. The following are 9 dazzling dynamic maps:

Endocytosis in human stem cell derived organs

Organelle dynamics in the brain of early zebrafish

Next step plan
Finally, it is worth mentioning that this device currently needs a table of 3 meters long, and Dr. Betzig is working to make it smaller and more humane. “The only criterion to judge the value of a microscope is the importance of how many people can use it and what people find with it.” He said. Ultimately, Dr Betzig hopes that this new technology can be commercialized and make adaptive optics the mainstream.


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