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Analytical Chemistry

Seeing Through Biological Tissue

New, inexpensive optical clearing formula makes tissue samples transparent to light

by Lauren K. Wolf
September 19, 2011 | A version of this story appeared in Volume 89, Issue 38

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Credit: Nat. Neurosci.
A mouse embryo soaked in the optical clearing agent Scale for two weeks becomes transparent (right) while an embryo soaked in buffer remains opaque (left).
Credit: Nat. Neurosci.
A mouse embryo soaked in the optical clearing agent Scale for two weeks becomes transparent (right) while an embryo soaked in buffer remains opaque (left).

Neuroscientists struggling to map neural connections in the brain have a new tool to help them in their endeavor, according to a Nature Neuroscience report (DOI: 10.1038/nn.2928). A team of researchers led by Atsushi Miyawaki of RIKEN, Japan’s research institute near Tokyo, has developed an optical clearing reagent that renders tissue samples transparent to light. Because neurons are slender and project extensively throughout brain tissue, which typically blocks light transmission past a depth of about 100 µm, it is difficult to image fluorescently tagged neurons. ­Miyawaki’s team, however, produced a urea-, glycerol-, and surfactant-based solution it calls Scale that makes whole mouse brains and embryos transparent to a depth of several millimeters yet preserves fluorescence signals from labeled cells. “One caveat of Scale is that it takes several days to clear tissues and doubles the tissue volume,” says Ann-Shyn Chiang, a brain researcher at Taiwan’s National Tsing Hua University who previously developed the faster-acting clearing agent FocusClear. Miyawaki and coworkers hope that by tinkering with their less expensive reagent’s composition, they can improve these properties.

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