Super-resolution endoscopy for real-time widefield imaging

Resolving subcellular structures in vitro beyond optical diffraction barrier by a light microscope has achieved significant development since the advancement of super-resolution fluorescence microscopes, such as stimulated emission depletion (STED) microscopy, stochastic optical reconstruction microscopy (STORM) and photoactivated localization microscopy (PALM). However, the resolution of observation in deep and dense in vivo tissues is still confined to cellular level presently, and hence, exploring image details at subcellular level or even beyond organelle level in vivo has continued to attract much research attention. Currently, endoscopy provides an effective way to achieve in vivo observations and is compatible with mature optical microscopy technologies, but its resolution is usually confined to ∼1 μm. Here we report a new endoscopy method by functionalizing graded-index (GRIN) lens with microspheres for real-time white-light or fluorescent super-resolution imaging. The capability of resolving objects with feature size of ∼λ/5, which breaks the diffraction barrier of traditional GRIN lens based endoscopes by a factor of two, has been demonstrated by using this superresolution endoscopy method. Further development of such a superresolution endoscopy technique may provide new opportunities for in vivo life sciences studies.