Hsiao, Fu-TingFu-TingHsiaoChien, Hung-JenHung-JenChienChou, Ya-HsienYa-HsienChouPeng, Shih-JungShih-JungPengChung, Mei-HsinMei-HsinChungHuang, Tzu-HuiTzu-HuiHuangLo, Li-WenLi-WenLoShen, Chia-NingChia-NingShenChang, Hsiu-PiHsiu-PiChangCHIH-YUAN LEECHIEN-CHIA CHENYUNG-MING JENGYU-WEN TIENTang, Shiue-ChengShiue-ChengTang2023-07-122023-07-122023-06-092041-1723https://scholars.lib.ntu.edu.tw/handle/123456789/633546Optical clearing with high-refractive-index (high-n) reagents is essential for 3D tissue imaging. However, the current liquid-based clearing condition and dye environment suffer from solvent evaporation and photobleaching, causing difficulties in maintaining the tissue optical and fluorescent features. Here, using the Gladstone-Dale equation [(n-1)/density=constant] as a design concept, we develop a solid (solvent-free) high-n acrylamide-based copolymer to embed mouse and human tissues for clearing and imaging. In the solid state, the fluorescent dye-labeled tissue matrices are filled and packed with the high-n copolymer, minimizing scattering in in-depth imaging and dye fading. This transparent, liquid-free condition provides a friendly tissue and cellular environment to facilitate high/super-resolution 3D imaging, preservation, transfer, and sharing among laboratories to investigate the morphologies of interest in experimental and clinical conditions.en[SDGs]SDG3[SDGs]SDG15journal article10.1038/s41467-023-39082-4372961172-s2.0-85163051609https://api.elsevier.com/content/abstract/scopus_id/85163051609