A new study from the Imai Group has been published in Nature Methods. In this work, the team developed SeeDB-Live, an optical clearing reagent that enables deep-tissue imaging of living samples while maintaining normal cellular function. The researchers discovered that the primary reason living tissues appear opaque is that light is refracted and scattered both inside and outside cells, preventing it from traveling straight. They demonstrated that adding albumin, a type of protein, to the extracellular solution suppresses this refraction and scattering, allowing non-invasive optical clearing of living tissues. Albumin minimally alters the ionic composition of the extracellular fluid and is non-toxic to cells. As a result, this method makes it possible for the first time to observe the normal functions of cells within cleared living tissues using fluorescence microscopy.
Using SeeDB-Live, which employs albumin as its key component, the team successfully achieved non-invasive clearing of excised brain tissue as well as the brains of living mice. This enabled high-resolution observation of fine structures and neuronal activity deep within the tissue. The findings open the door to measuring physiological functions in deep tissue regions—something that has long been challenging—and are expected to contribute significantly to the advancement of neuroscience, developmental biology, and a wide range of life science fields.
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Press Release : https://www.kyushu-u.ac.jp/en/researches/view/375
Nature Methods : https://doi.org/10.1038/s41592-026-03023-y
