Tainaka, K. et al. Cell Rep. 24, 2196–2210 (2018).
Tissue-clearing technologies improve optical access to scattering tissue such as brain. Although a number of different approaches are available, their development typically has been serendipitous and did not necessarily follow a rational strategy. Tainaka et al. screened a collection of about 1,600 hydrophilic chemical compounds for favorable performance in delipidation, decolorization, refractive index matching and decalcification assays. The researchers then combined promising compounds into several different CUBIC (clear, unobstructed brain/body imaging cocktails and computational analysis) cocktails designed to achieve good performance in bone clearing, human brain clearing, or fast clearing, or to preserve fluorescence in tissues expressing fluorescent proteins. The various CUBIC cocktails can be mixed and matched in accordance with experimental needs. The researchers demonstrated their updated CUBIC protocols by clearing whole mice, large human tissue samples, and a marmoset brain.