Nanosilver-Enhanced\nFar-Field Fluorescence Fluctuations\nfor Super-Resolution Microscopy

Fluctuation-based super-resolution microscopy enhances\nimage resolution\nusing signal fluctuations, yet the inherent fluctuations of fluorophores\nlimit its spatiotemporal resolution. In this work, we reveal a far-field\nenhancement (FFE) effect via a nanosilver film that significantly\nboosts fluorescence fluctuations of fluorophores positioned up to\n10 μm away. The FFE effect arises from the interference of scattered\nlight from the nanosilver film and photothermal-induced refractive\nindex changes in the imaging medium, which create periodic auxiliary\nillumination on the sample. This phenomenon enabled the development\nof far-field enhanced super-resolution microscopy (FFE-SRM), a technique\ncompatible with commonly used fluorophores. FFE-SRM improves temporal\nresolution up to 10-fold and enhances spatial resolution by about\n2-fold over various SRM methods, including stochastic optical fluctuation\nimaging, super-resolution radial fluctuation, mean-shift super-resolution,\nand direct stochastic optical reconstruction microscopy. We demonstrated\nthe potential of FFE-SRM by revealing mitochondrial dynamics in live-cell\nimaging, advancing super-resolution imaging, and cellular process\nexploration.