Many clearing methods achieve high transparency by removing lipid components from tissues, which damages microstructure and limits their application in lipid research. As for methods which preserve lipid, it is difficult to balance transparency, fluorescence preservation and clearing speed. In this study, we propose a rapid water-based clearing method that is fluorescence-friendly and preserves lipid components. FLUID allows for preservation of endogenous fluorescence over 60 days. It shows negligible tissue distortion and is compatible with various types of fluorescent labeling and tissue staining methods. High quality imaging of human brain tissue and compatibility with pathological staining demonstrated the potential of our method for three-dimensional (3D) biopsy and clinical pathological diagnosis.
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