  Super-resolution microscopy is providing unprecedented insights into biology
by resolving details much below the diffraction limit. State-of-the-art Single
Molecule Localization Microscopy (SMLM) techniques for super-resolution are
restricted by long acquisition and computational times, or the need of special
fluorophores or chemical environments. Here, we propose a novel statistical
super-resolution technique of wide-field fluorescence microscopy called
MUltiple SIgnal Classification ALgorithm (MUSICAL) which has several advantages
over SMLM techniques. MUSICAL provides resolution down to at least 50 nm, has
low requirements on number of frames and excitation power and works even at
high fluorophore concentrations. Further, it works with any fluorophore that
exhibits blinking on the time scale of the recording. We compare imaging
results of MUSICAL with SMLM and four contemporary statistical super-resolution
methods for experiments of in-vitro actin filaments and datasets provided by
independent research groups. Results show comparable or superior performance of
MUSICAL. We also demonstrate super-resolution at time scales of 245 ms (using
49 frames at acquisition rate of 200 frames per second) in samples of live-cell
microtubules and live-cell actin filaments.
