Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents
Author(s) -
Kazuki Tainaka,
Tatsuya C. Murakami,
Etsuo A. Susaki,
Chika Shimizu,
Rie Saito,
Kei Takahashi,
Akiko HayashiTakagi,
Hiroshi Sekiya,
Yasunobu Arima,
Satoshi Nojima,
Masako Ikemura,
Tetsuo Ushiku,
Yoshihiro Shimizu,
Masaaki Murakami,
Kenji F. Tanaka,
Masamitsu Iino,
Haruo Kasai,
Toshikuni Sasaoka,
Kazuto Kobayashi,
Kohei Miyazono,
Eiichi Morii,
Tadashi Isa,
Masashi Fukayama,
Akiyoshi Kakita,
Hiroki R. Ueda
Publication year - 2018
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2018.07.056
Subject(s) - chemistry , partition coefficient , chemical imaging , amide , reagent , combinatorial chemistry , organic chemistry , computer science , artificial intelligence , hyperspectral imaging
We describe a strategy for developing hydrophilic chemical cocktails for tissue delipidation, decoloring, refractive index (RI) matching, and decalcification, based on comprehensive chemical profiling. More than 1,600 chemicals were screened by a high-throughput evaluation system for each chemical process. The chemical profiling revealed important chemical factors: salt-free amine with high octanol/water partition-coefficient (logP) for delipidation, N-alkylimidazole for decoloring, aromatic amide for RI matching, and protonation of phosphate ion for decalcification. The strategic integration of optimal chemical cocktails provided a series of CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) protocols, which efficiently clear mouse organs, mouse body including bone, and even large primate and human tissues. The updated CUBIC protocols are scalable and reproducible, and they enable three-dimensional imaging of the mammalian body and large primate and human tissues. This strategy represents a future paradigm for the rational design of hydrophilic clearing cocktails that can be used for large tissues.
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