Researchers at Juntendo University have developed a novel 3D immunohistochemistry technique enhancing rapid and deep tissue imaging, significantly reducing traditional processing times. The method employs single-domain camelid-derived nanobodies fused with horseradish peroxidase enzymes and a fluorescent tyramide-glucose oxidase signal amplification system (POD-nAb/FT-GO), facilitating improved penetration and ultra-high resolution visualization of neural and glial structures within thick brain samples. This platform overcomes limitations of conventional antibodies, allowing efficient labeling deep in tissues, enhancing neuroscientific research capabilities and pathology diagnostics in complex specimens.