ClearGel: a thermoresponsive hydrogel for chronic, near-millimeter two-photon imaging through the intact skull

ClearGel, a thermoresponsive hydrogel applied on intact mouse skulls, enables two-photon imaging to ~800 m depth, matching open-skull windows and exceeding prior approaches.

• Why it matters: The intact skull blocks high-resolution two-photon neuroimaging, and existing clearing methods fail to combine deep access, spatial targeting, reversibility, and biological safety for chronic use.
• What they did: The team used a hydrogel that rapidly gels in situ on skull contact to localize clearing agents and sustain their release, then performed longitudinal two-photon imaging and awake functional measurements.
• The result: ClearGel supports user-defined clearing patterns, repeated imaging for 14 days via a reversible optical interface, and awake single-cell Ca2+ and cAMP dynamics imaging through the intact skull.

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