A research team led by Kim Dong-hyun, a professor in the Department of Electrical and Electronic Engineering at Yonsei University, said on the 23rd that it has developed a new imaging technology that solves the limitations of existing three-dimensional super-resolution microscopes with a simple structure.
Existing three-dimensional super-resolution microscopes can observe cells in fine detail, but they have a problem of low resolution in the depth (vertical, Z-axis) direction. Because of this, cell structures appeared elongated and distorted compared to reality. There had been several attempts to compensate for this, but the equipment setups were excessively complex or the manufacturing costs were too high to move beyond the laboratory level.
The new device developed by the team is "AXIS-SIM (mirror-interference-based three-dimensional super-resolution microscope)." True to its name, it is implemented in a simple way by adding just one mirror to the existing microscope structure.
When light reflected from the mirror interferes with a specialized patterned illumination, highly precise illumination is formed even in the depth direction (Z-axis). Using this generated light makes it possible to observe the cell interior in three dimensions much more clearly.
As a result, the team achieved a resolution of 108.5 nanometers (nm) in the horizontal direction and 140.1 nanometers in the depth (vertical) direction. This is more than twice as good as existing technology (about 300 nm), and it is a world-class achievement that realizes an "isotropic" three-dimensional image with almost no difference between horizontal and vertical resolution.
Using this technology, the team succeeded in high-resolution observation of microtubules and lysosomes (organelles that degrade cellular waste) inside living cancer cells. They tracked in real time the movement of lysosomes inside cells at a speed of 79 nanometers per second and even captured the void structures inside lysosomes, opening new possibilities for research on intracellular organelles.
The researchers said, "It is significant that we solved a long-standing challenge in three-dimensional super-resolution imaging with a simple structure that adds just one mirror," and noted, "This technology can expand not only to new drug development and identifying disease causes but also to next-generation optical research such as quantum optics and quantum imaging, which precisely handle the principle of light interference."
The researchers said, "It is meaningful that we solved the challenge of three-dimensional super-resolution imaging in a simple way without complex and expensive equipment," and added, "Because this technology precisely leverages the principle of light interference, it can contribute to new drug development and identifying disease causes, and it could also expand into next-generation research fields such as quantum optics and quantum imaging."
The study was published on the 20th in the international journal "Nature Communications." Related technology research was recently featured in "Nature Photonics."
References
Nat Commun (2025), DOI: https://doi.org/10.1038/s41467-025-64366-2