Anisotropy enables advanced light sheet microscopy with opaque lenses

Abstract: Advances in fluorescence microscopy have reached a plateau in improving depth-to-resolution ratios for imaging scattering tissues, highlighting an urgent need for innovative techniques. We introduce Wavelens, a groundbreaking opaque lens that combines dynamic wavefront shaping with a passive, angularly anisotropic photonic scattering plate-designed to scatter light predominantly in one direction. This compact, robust optoelectronic device, comparable in size to a conventional microscope lens, delivers superior light sheet formation capabilities. Using Wavelens, we achieved high-resolution LSFM imaging of diverse biological specimens, including 3D tumor spheroids and the intricate neural architecture of Caenorhabditis elegans in vivo. Notably, Wavelens maintains consistent light sheet properties even in dense, scattering-prone samples, overcoming a long-standing limitation of traditional microscopy. This innovative approach has the potential to revolutionize optical imaging, offering unprecedented clarity and resilience, even within dense, scattering-prone biological samples.