Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Aug 21;24(8):2196-2210.e9.
doi: 10.1016/j.celrep.2018.07.056.

Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents

Free article

Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents

Kazuki Tainaka et al. Cell Rep. .
Free article


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.

Keywords: chemistry in tissue clearing; comprehensive chemical profiling; high-throughput chemical screening; hydrophilic reagents; three-dimensional imaging; virtual multiplex imaging.

Comment in

  • Shaking up clearing cocktails.
    Vogt N. Vogt N. Nat Methods. 2018 Nov;15(11):859. doi: 10.1038/s41592-018-0199-4. Nat Methods. 2018. PMID: 30377353 No abstract available.

Similar articles

See all similar articles

Cited by 14 articles

See all "Cited by" articles

Publication types

MeSH terms


LinkOut - more resources