SMartS · Super-resolution Fluorescence Microscopy based on Artificial Mesoscopic Structures

Studies of the dynamical process of biological samples benefits from real-time imaging microscopy which can provide wide-field high resolution with sufficient material contrast. Hence, fluorescence-based microscopy has become one of the essential tools of modern biology. However, fluorescence techniques as other optical tool suffer from a fundamental resolution limit due to the wave nature of light. While resolution is denoted by the ability to discern different objects, much effort has been devoted to improve the spatial resolution of far-field fluorescence microscopy and it has spurred the emergence of many innovative techniques. Stimulated Emission Depletion (STED) microscopy has shown the best lateral resolution among the far-field techniques. However, based on point scanning, it is too slow to catch fast molecular dynamics in an image time series. Photo-activated localization microscopy (PALM) and stochastic optical reconstruction microscopy (STORM) are equally powerful techniques that strictly spoken do not improve the spatial resolution, but the localization precision to pinpoint single molecules. The major drawback is that image acquisition is time consuming and thus makes them even less compatible for fast real-time imaging. Henceforth, the lifesciences community is still missing a microscopy technique that provides both high speed and super-resolution. To hurdle these limitations, we propose a fluorescence method that is based on artificial mesoscopic structures that are fully biocompatible and allow for super-resolution imaging of molecular dynamics in live cell with video-rate acquisition speed. Using an artificial mesoscopic structure one can manipulate light and design new components not previously realized such as a “perfect lens”. It has the potential for a breakthrough in biotechnology and may close the gap between Electron Microscopy (EM) and Fluorescence Microscopy (FM) even further to link structure and function of a biomolecule respectively.