Unclearing Microscopy
M'Saad, O.; Shribak, M.; Bewersdorf, J.
10.1101/2022.11.29.518361 bioRxivShow abstract
The spatial resolution and contrast sensitivity of the human eye is limited, restricting our ability to directly see subcellular structures. We report a new principle for unaided eye cellular visualization in a method we call Unclearing Microscopy. By expanding cells and tissue >8,000 volumetrically and opaquing their bulk with light-scattering molecules of sufficient density, cell microstructure can now be discerned with a contrast visible to the unaided eye. We further inspect uncleared samples with transmitted light microscopy modalities and prove that 3D ultrastructural features, previously accessible only with super-resolution fluorescence or electron microscopy methods, can now be visualized with simple magnification optics alone.
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