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.
Competing Interest Statement
J.B. has financial interests in Bruker Corp. and Hamamatsu Photonics. O.M. and J.B. filed patent applications with the U.S. Patent and Trademark Office covering the presented method. O.M. and J.B. are co-founders of panluminate Inc. which is developing related products.
