Tsinghua Team Proposes LA-SIM: 3D Super-Resolution Imaging That 'Illuminates' More Gently
Tsinghua Team Proposes LA-SIM: 3D Super-Resolution Imaging That 'Illuminates' More Gently
In super-resolution microscopy, "seeing clearly" and "seeing for long" have long been a contradiction: to resolve nanoscale structures, the sample must be illuminated with sufficiently strong light; but once the light is strong, live cells are easily damaged and the fluorescent molecules bleach. How to strike a balance between the two is one of the core challenges of live-cell imaging.
On September 28, 2026, the research group of Professor Li Dong at the School of Life Sciences, Tsinghua University, published in Nature Photonics a new technique called LA-SIM, attempting to give its own answer.
1. Slicing Light to Illuminate a Single Layer
LA-SIM's first move is to switch to sheet illumination. The team used a 405-nanometer lattice light sheet to illuminate only the thin layer to be observed, keeping the layers above and below dark. This not only reduces unnecessary illumination but also "calls by name" the reversibly photoswitchable fluorescent proteins near the focal plane—molecules elsewhere stay "pretending to sleep," and by not emitting light they are less easily damaged.
2. A 'Hollow' Beam Narrows the Glowing Layer
Illuminating just one layer is not enough. The team added a 488-nanometer beam whose center is empty, specially tasked with "switching off" the excess fluorescence on both sides of the activated thin layer, squeezing the truly emitting region even thinner. In this way, cells spend most of their time in the dark and naturally "do not tire, are not damaged, and live longer."
3. Results: 87-nm Resolution, ~2.5 h Imaging
The paper reports that LA-SIM raises the lateral resolution of 3D super-resolution imaging to about 87 nanometers; in the experimental demonstration, an intact mouse embryo was observed continuously under the lens for about two and a half hours while remaining in good condition. Seeing the details clearly without "ruining them"—this is precisely the direction that live-cell imaging pursues.
4. Significance
For life-science research, observing the subcellular structures of living samples over long periods with low damage means that many processes previously capturable only as a "single portrait" can become "a whole film." The arrival of LA-SIM offers a "gentler" option for live-cell 3D super-resolution imaging and brings people one step closer to seeing clearly the dynamic world inside cells.