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Updated: Jun 2, 2026

06:52
Optical Clearing and Labeling for Light-sheet Fluorescence Microscopy in Large-scale Human Brain Imaging
Published on: January 26, 2024
SynClear: A one-step synchronous clearing and labeling strategy for multiscale 3D brain mapping.
Xiao Xiao1,2,3, Canyu Ma4, Yashuo Wang4
1Department of Neurology of the Second Affiliated Hospital of Zhejiang University School of Medicine, State Key Laboratory of Extreme Photonics and Instrumentation & Liangzhu Laboratory, Zhejiang University, Hangzhou, 310058, China.
Materials Today. Bio
|June 1, 2026
Summary
SynClear integrates nuclear labeling and tissue clearing into one step, enabling rapid, uniform, and deep 3D imaging of biological tissues. This advance improves throughput and resolution for neuroscience and pathology applications.
Area of Science:
- Biotechnology
- Neuroscience
- Pathology
Background:
- High-resolution 3D imaging of biological tissues requires efficient clearing and molecular labeling.
- Current methods face kinetic mismatches, limiting imaging depth, uniformity, and throughput.
Purpose of the Study:
- To introduce SynClear, a novel one-step method synchronizing nuclear labeling with tissue clearing.
- To overcome limitations of conventional separate-step workflows in volumetric tissue imaging.
Main Methods:
- SynClear embeds fluorescent probes within a chemically engineered clearing medium for simultaneous labeling and clearing.
- The method was tested on diverse tissues: mouse brain, peripheral organs, and human cortex.
Main Results:
- SynClear achieved rapid and uniform labeling across millimeter-scale samples, preserving endogenous fluorescence.
- It enabled accurate 3D atlas registration, cytoarchitecture mapping, and analysis of pathological features in glioblastoma models.
- Applications in human cortex included laminar-resolved structural analysis and neuronal subtype mapping.
Conclusions:
- SynClear offers a robust and scalable platform for volumetric tissue imaging by integrating labeling and clearing.
- This approach has significant potential for advancing basic neuroscience research and translational pathology.

