The development of super-resolution fluorescence microscopy is very essential for understanding the physical and biological fundamentals at nanometer scale.However,to date most super-resolution modalities require either complicated/costly purpose-built systems such as multiple-beam architectures or complex post-processing procedures with intrinsic artifacts.Achieving three-dimensional(3D)or multi-channel sub-diffraction microscopic imaging using a simple method remains a challenging and struggling task.Herein,we proposed 3D highly-nonlinear super-resolution microscopy using a singlebeam excitation strategy,and the microscopy principle was modelled and studied based on the ultrahigh nonlinearity enabled by photon avalanches.According to the simulation,the point spread function of highly nonlinear microscopy is switchable among different modes and can shrink three-dimensionally to sub-diffraction scale at the photon avalanche mode.Experimentally,we demonstrated 3D optical nanoscopy assisted with huge optical nonlinearities in a simple laser scanning configuration,achieving a lateral resolution down to 58 nm(λ/14)and an axial resolution down to 185 nm(λ/5)with one single beam of low-power,continuous-wave,near-infrared laser.We further extended the photon avalanche effect to many other emitters to develop multi-color photon avalanching nanoprobes based on migrating photon avalanche mechanism,which enables us to implement single-beam dual-color sub-diffraction super-resolution microscopic imaging.
