Kyushu University Develops Albumin-Based SeeDB-Live Reagent to Achieve Real-Time Transparent Imaging of the Living Brain

Kyushu University researchers use blood protein to make living brains transparent, allowing for deep, real-time imaging of neuronal activity in mice.

By: AXL Media

Published: Mar 12, 2026, 11:00 AM EDT

Source: Information for this report was sourced from Kyushu University

Achieving Optical Transparency in Functional Neural Tissue

Researchers at Kyushu University have broken a decade-long technical barrier by developing a method to make living brain tissue transparent for high-resolution imaging. Traditionally, the brain’s opaque nature, caused by light scattering between lipids and cellular components, has limited how deep scientists can observe active neurons. The new reagent, SeeDB-Live, solves this by equalizing the refractive index of the extracellular environment with that of the cells. According to Professor Takeshi Imai, this is the first time tissue clearing has been achieved without altering the underlying biology, allowing for the observation of neurons as they fire in real-time.

The Physics of Light Refraction and Brain Opacity

The fundamental challenge of deep-brain imaging is rooted in optics, specifically how light refracts when passing through materials with different indices. Much like how glass marbles become invisible when submerged in oil of a matching refractive index, brain tissue becomes clear when the surrounding fluid matches the internal cellular index of 1.36 to 1.37. Previous attempts to achieve this transparency relied on high concentrations of sugar, which created excessive osmotic pressure and dehydrated the cells. By identifying the precise refractive target, the Kyushu team sought a polymer that could achieve clarity without triggering the toxic swelling or shrinking of sensitive neural structures.

Serendipitous Discovery of Albumin as a Clearing Agent

The breakthrough occurred when Assistant Professor Shigenori Inagaki experimented with bovine serum albumin (BSA), a common protein found in blood serum. Unlike synthetic polymers, this blood-derived protein exhibited the lowest osmotic pressure at the required refractive index, making it the ideal medium for preserving cell life. Inagaki noted that the discovery was unexpected, emerging from a late-night session in the lab where he tested high-purity albumin as a last resort. This natural polymer allows the reagent to reach the necessary optical performance while maintaining a delicate ionic balance, a feat that nearly 100 other screened compounds failed to accomplish.