observation that led to Scale, his urea-based clearing agent. It removes lipids with detergents rather than with organic solvents and then hydrates tissue. A new sorbitol and urea–based version called ScaleS is gentler, says Miyawaki, and it preserves membrane structures well. Thus, for example, fluorescent proteins tethered to the plasma membrane will get along well with ScaleS, he says, which will help labs that place FPs beneath the plasma membrane to enable neuronal tracing. ScaleS will work with any fixation-resistant probes, he says. His team is using this clearing agent to compare proliferation and differentiation in fluorescent ubiquitinationbased cell cycle indicator transgenic mice. To avoid FP quenching and to lessen scatter by making the tissue more homogeneous, labs have developed clearing agents that do not apply detergents or solvents, such as SeeDB and ClearT. But clearing large samples this way can take many weeks.