Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents
Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents
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DOI：
10.1016/j.celrep.2018.07.056
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发表时间：
2018-08-21
期刊：
影响因子：
8.8
通讯作者：
Ueda, Hiroki R.
中科院分区：
文献类型：
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作者：
Tainaka, Kazuki;Murakami, Tatsuya C.;Ueda, Hiroki R.
我们描述了一种策略，开发亲水性化学鸡尾酒组织脱脂，脱色，折射率（RI）匹配，脱钙，综合化学分析的基础上。每种化学工艺都通过高通量评估系统筛选了1，600多种化学品。化学剖析揭示了重要的化学因素：无盐胺与高辛醇/水分配系数（logP）的脱脂，N-烷基咪唑脱色，芳香酰胺的RI匹配，和质子化的磷酸根离子脱钙。最佳化学鸡尾酒的战略整合提供了一系列CUBIC（清晰，无障碍的大脑/身体成像鸡尾酒和计算分析）协议，可以有效地清除小鼠器官，小鼠身体（包括骨骼），甚至大型灵长类动物和人体组织。更新的CUBIC协议是可扩展和可再现的，它们能够对哺乳动物身体和大型灵长类动物和人类组织进行三维成像。该策略代表了可用于大组织的亲水性清除鸡尾酒的合理设计的未来范例。
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.