By Julian Namerow, Class of 2026
The human body is composed of organ systems that span far, intricately, and seamlessly to perform essential biological functions, such as the neurons that span to the tips of one’s toes and trace all the way back through the spinal cord to the brain. Current methods for understanding large-scale tissue architecture at microstructural resolutions are challenging. They involve tissue dehydration, rehydration, and another dehydration, thinly slicing the tissue, aqueous staining—where dyes bind selectively to different tissue components to make them distinguishable under a microscope—and lastly, a xylene wash. Finally, your slice of tissue can be mounted and examined under the microscope, but due to the extensive preparation, the biomolecules are denatured and undergo severe shrinking. It is also challenging to precisely reconstruct the 3D structure based on the slices.
Introduced in this research is vitreous ionic-liquid-solvent-based volumetric inspection of trans-scale biostructures (VIVIT), which transforms biological tissue into an ionic glassy state. This allows researchers to take an organ such as the brain, submerge it in the VIVIT, transforming the tissue into a transparent gelatinous state. In practice, the neurons can be immunofluorescently stained and studied within the intact organ. The ionic glassy state of the tissue enables great optical clearing, with minimal distortion and high transparency, especially for immunofluorescent signals, which are enhanced through VIVIT. This method yields precise and reliable mapping of fluorescent signals with intact 3D biological architectures.
The lab demonstrated the paths of various synaptic inputs to thalamic neurons and located the targets of its brain-wide output signal. Their results also suggested distinct inhibitory patterns different from those established in mice and other non-human species, suggesting that the synapse organization remains inadequately verified in the human cortex.
Multiple solvents that achieve the same goals were introduced; though they are non-conventional solvents for histology, they are typically non-volatile, non-toxic, environmentally friendly, and easily tunable for various chemical and physical properties of the body. However, the mechanisms underlying VIVIT are still unknown. Investigations must be done to understand the interactions and reactions occurring and to truly understand VIVIT’s potential. VIVIT efficiently reveals the structure information of brain-wide outputs and synapse-level inputs.
Work’s Cited:
Gao, Y., Xin, F., Wang, T., Shao, C., Hu, Y., Chen, Z., Wang, Y., Xie, F., Li, T., Li, S., Ren, L., Li, C., Yang, X., Yang, Z., Li, M., Tan, K., Bai, T., Wei, C., Peng, H., Li, K., … Yuan, K. (2025). VIVIT: Resolving trans-scale volumetric biological architectures via ionic glassy tissue. Cell, 188(21), 6079–6095.e20.
