Journal
CELL REPORTS
Volume 24, Issue 8, Pages 2196-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.07.056
Keywords
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Funding
- AMED-CREST (AMED/MEXT)
- CREST (JST/MEXT) [JPMJCR1652]
- PRESTO from JST [JPMJPR15F4]
- Brain/MINDS (AMED/MEXT)
- Basic Science and Platform Technology Program for Innovative Biological Medicine (AMED/MEXT)
- Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemic (AMED) [JP17fm0208023]
- Strategic Research Program from Brain Sciences (AMED) [JP18dm0107120]
- JSPS KAKENHI [16K15124, 15H05650, 16J05041, 25221004, 18H05270, 26221001, 18H02105, 18H02540]
- MEXT [23115006, 17H05688, 18H04543, 17H06328]
- Naito Science & Engineering Foundation
- Tokyo Biochemical Research Foundation
- Cell Science Research Foundation
- NOVARTIS Foundation (Japan) for the Promotion of Science
- Takeda Science Foundation
- Japan Foundation for Applied Enzymology
- Brain Sciences Project of the Center for Novel Science Initiatives of the National Institutes of Natural Sciences [BS291001]
- Grants-in-Aid for Scientific Research [18H02105, 17H06328, 18H02540, 18H05270, 17H05688, 15H05650, 16J05041, 16K15124, 18H04543] Funding Source: KAKEN
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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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