Making a living brain transparent and observing neurons firing in real time without affecting their activity may sound like science fiction. However, researchers now believe that the answer may lie in a substance naturally present in the human body.
In a study published on March 12, 2026 in Nature Methods, scientists from Kyushu University introduced a novel reagent known as SeeDB-Live. The method uses Albumin, a common protein found in blood serum, to temporarily clear brain tissue while preserving normal cellular activity.
The research team, led by Takeshi Imai, demonstrated that the technique allows researchers to observe deeper neural structures in both cultured brain slices and living mice. For the first time, tissue transparency has been achieved without altering biological processes.
According to the study’s first author, Shigenori Inagaki, SeeDB-Live could significantly advance deep-tissue imaging in both ex vivo and in vivo experiments.
The brain normally appears opaque because microscopic differences in refractive indices between cellular components scatter incoming light. Lipids and other structures disrupt light transmission, preventing scientists from visualizing deeper neural layers.
Through extensive experimentation, the researchers discovered that brain cells become significantly clearer when the refractive index of the surrounding solution is adjusted to approximately 1.36–1.37.
After testing numerous chemical compounds, the researchers unexpectedly discovered that bovine serum albumin produced the desired optical conditions while maintaining proper osmotic balance for living cells.
When incorporated into the culture medium, albumin created a live-tissue clearing solution named SeeDB-Live. The reagent was able to render mouse brain slices transparent within about one hour.
Using fluorescence calcium indicators, the team observed neuronal activity deep inside the tissue. In living mouse brains, fluorescence signals from neurons became roughly three times brighter.
This allowed researchers to visualize neurons in layer 5 of the cerebral cortex, a region involved in processing and transmitting neural information.
Unlike many existing clearing techniques, SeeDB-Live does not permanently modify tissue. Once the reagent is washed away, the brain gradually returns to its original opaque state, allowing repeated imaging of the same animal over time.
Researchers believe this approach may greatly enhance deep fluorescence imaging and improve the study of neural networks, brain organoids, and drug discovery models.
