Uncovering Why Tissue Shrinks During Optical Clearing

Tissue clearing allows researchers to visualize complex structures, such as brain-wide neural pathways, in three dimensions—even in entire mouse specimens. Yet, despite its long history, the physical processes underlying tissue clearing are still not fully understood.

In a newly published study, “On the Molecular Basis of Shrinkage in Hydrophobic Tissue Clearing,” a team around Zernike colleagues van der Giessen, van der Wel and van der Zaag shows that tissue shrinkage during BABB-based clearing is linked to protein content and changes in electrostatic interactions, driven in part by changes in the tissue’s dielectric properties as water is replaced by organic solvents.

This insight provides a new understanding of a long-standing challenge in tissue clearing and an important first step toward exploring its potential clinical applications. In collaboration with UMCG, the researchers are investigating whether tissue clearing could help surgeons assess tumour margins more accurately during fluorescence-guided surgery.

Reference: On the Molecular Basis of Shrinkage in Hydrophobic Tissue Clearing, Ali Fakhrolmobasheri; Pushpa Rampratap; Alwin Jansen; Marco van den Noort; Zhongyang Zhang; Bert Poolman; E. van der Giessen; Patrick C.A. van der Wel; P.J. van der Zaag, Chemical & Biomedical Imaging (2026), https://doi.org/10.1021/cbmi.6c00155