  Here we report nonlinear focal modulation microscopy (NFOMM) to achieve
super-resolution imaging. Abandoning the previous persistence on minimizing the
size of Gaussian emission pattern by directly narrowing (e.g. Minimizing the
detection pinhole in Airyscan, Zeiss) or by indirectly peeling its outer
profiles (e.g., Depleting the outer emission region in STED, stimulated
emission microscopy) in pointwise scanning scenarios, we stick to a more
general basis------ maximizing the system frequency shifting ability. In NFOMM,
we implement a nonlinear focal modulation by applying phase modulations with
high-intensity illumination, thereby extending the effective spatial-frequency
bandwidth of the imaging system for reconstructing super-resolved images. NFOMM
employs a spatial light modulator (SLM) for assisting pattern-modulated
pointwise scanning, making the system single beam path while achieving a
transverse resolution of 60 nm on imaging fluorescent nanoparticles. While
exploring a relatively simple and flexible system, the imagingperformance of
NFOMM is comparable with STED as evidenced in imaging nuclear pore complexes,
demonstrating NFOMM is a suitable observation tool for fundamental studies in
biology. Since NFOMM is implemented as an add-on module to an existing laser
scanning microscope and easy to be aligned, we anticipate it will be adopted
rapidly by the biological community.
