Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents

Kazuki Tainaka, Tatsuya C. Murakami, Etsuo A. Susaki, Chika Shimizu, Rie Saito, Kei Takahashi, Akiko Hayashi-Takagi, 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 MiyazonoEiichi Morii, Tadashi Isa, Masashi Fukayama, Akiyoshi Kakita, Hiroki R. Ueda

Research output: Contribution to journalArticle

40 Citations (Scopus)

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. Tainaka et al. describe a strategy for developing hydrophilic tissue-clearing reagents based on comprehensive chemical profiling. The strategic integration of optimal chemical cocktails provided a series of CUBIC protocols, which enable the 3D imaging of the mammalian body and large primate and human tissues.

Original languageEnglish
Pages (from-to)2196-2210.e9
JournalCell Reports
Volume24
Issue number8
DOIs
Publication statusPublished - 2018 Aug 21

Keywords

  • chemistry in tissue clearing
  • comprehensive chemical profiling
  • high-throughput chemical screening
  • hydrophilic reagents
  • three-dimensional imaging
  • virtual multiplex imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents'. Together they form a unique fingerprint.

  • Cite this

    Tainaka, K., Murakami, T. C., Susaki, E. A., Shimizu, C., Saito, R., Takahashi, K., Hayashi-Takagi, A., Sekiya, H., Arima, Y., Nojima, S., Ikemura, M., Ushiku, T., Shimizu, Y., Murakami, M., Tanaka, K. F., Iino, M., Kasai, H., Sasaoka, T., Kobayashi, K., ... Ueda, H. R. (2018). Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents. Cell Reports, 24(8), 2196-2210.e9. https://doi.org/10.1016/j.celrep.2018.07.056