Emerging and transformative applications of tissue clearing technology in neuroscience research
5 affiliations
- 1Chinese Institute for Brain Research, Beijing, China
- 2Naval Medical University, No.800, Xiangyin Road, Shanghai 200433, China
- 3Department of Biomedical Sciences, Cancer Research and Specialist Centre, Universiti Sains Malaysia, Penang 13200, Malaysia
- 4Chinese Institute for Brain Research, Beijing, China; Corresponding author
- 5Naval Medical University, No.800, Xiangyin Road, Shanghai 200433, China; Corresponding author
Abstract
Refractive index (RI)-matching-based tissue clearing techniques render intact biological tissues optically transparent, enabling 3D in situ interrogation of nervous systems from whole-brain to single-cell scales. We systematically evaluate three mainstream clearing strategies (hydrophobic, hydrophilic, and hydrogel-based) and summarize their promising applications in neural circuit tracing, tumor research, stem cell therapy, and artificial intelligence (AI) integration. Here, we report that this technology has evolved from a niche imaging tool to an integrated multimodal biotechnological platform. Despite core challenges, including inherent physicochemical trade-offs, optical limits, multi-omics integration biases, and insufficient clinical standardization, future advances in multimodal integration, AI algorithms, and targeted in vivo clearing will drive life science research from static structural mapping toward systematic dissection of dynamic biological processes.
Related
- Development of shelf-stable reagents and assay kits for bioluminescence applications using the capillary-assisted vitrification platform stabilization technology
- “White and Clear” (WaC): A tunable hydrophilic tissue clearing strategy for multi‐species 3D imaging
- The transformative impact of stem cell core facilities in biomedical research
- Biosensors as transformative tools for detection of lung cancer based on non-coding RNA
- Molecular origami in neuroscience: noncanonical DNA structures and functional nucleic acids in neural regulation and disease
BibTeX
@article{chen2026emerging,
title = {{Emerging and transformative applications of tissue clearing technology in neuroscience research}},
author = {Man-Yu Chen and Xuan Yin and Haoling Zhang and Lizhou Song and Hu Zhao and Wangzheqi Zhang},
journal = {Cell Reports Physical Science},
year = {2026},
month = oct,
doi = {10.1016/j.xcrp.2026.103607},
url = {https://doi.org/10.1016/j.xcrp.2026.103607},
note = {CC BY},
}
RIS
TY - JOUR
TI - Emerging and transformative applications of tissue clearing technology in neuroscience research
AU - Man-Yu Chen
AU - Xuan Yin
AU - Haoling Zhang
AU - Lizhou Song
AU - Hu Zhao
AU - Wangzheqi Zhang
PY - 2026
DA - 2026/10/30
JO - Cell Reports Physical Science
DO - 10.1016/j.xcrp.2026.103607
UR - https://doi.org/10.1016/j.xcrp.2026.103607
AB - Refractive index (RI)-matching-based tissue clearing techniques render intact biological tissues optically transparent, enabling 3D in situ interrogation of nervous systems from whole-brain to single-cell scales. We systematically evaluate three mainstream clearing strategies (hydrophobic, hydrophilic, and hydrogel-based) and summarize their promising applications in neural circuit tracing, tumor research, stem cell therapy, and artificial intelligence (AI) integration. Here, we report that this technology has evolved from a niche imaging tool to an integrated multimodal biotechnological platform. Despite core challenges, including inherent physicochemical trade-offs, optical limits, multi-omics integration biases, and insufficient clinical standardization, future advances in multimodal integration, AI algorithms, and targeted in vivo clearing will drive life science research from static structural mapping toward systematic dissection of dynamic biological processes.
SN - 2666-3864
ER -