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Title: Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents
Authors: Tainaka, Kazuki
Murakami, Tatsuya C.
Susaki, Etsuo A.
Shimizu, Chika
Saito, Rie
Takahashi, Kei
Hayashi-Takagi, Akiko
Sekiya, Hiroshi
Arima, Yasunobu
Nojima, Satoshi
Ikemura, Masako
Ushiku, Tetsuo
Shimizu, Yoshihiro
Murakami, Masaaki
Tanaka, Kenji F.
Iino, Masamitsu
Kasai, Haruo
Sasaoka, Toshikuni
Kobayashi, Kazuto
Miyazono, Kohei
Morii, Eiichi
Isa, Tadashi  kyouindb  KAKEN_id
Fukayama, Masashi
Kakita, Akiyoshi
Ueda, Hiroki R.
Author's alias: 伊佐, 正
Keywords: chemistry in tissue clearing
hydrophilic reagents
high-throughput chemical screening
comprehensive chemical profiling
three-dimensional imaging
virtual multiplex imaging
Issue Date: 21-Aug-2018
Publisher: Elsevier BV
Journal title: Cell reports
Volume: 24
Issue: 8
Start page: 2196
End page: 2210.e9
Abstract: 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.
Rights: © 2018 The Author(s). This is an open access article under the CC BY license (
DOI(Published Version): 10.1016/j.celrep.2018.07.056
PubMed ID: 30134179
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