Light sheet fluorescence microscopy (LSFM) is widely used in biological imaging because of its low photobleaching and phototoxicity. The axial resolution of LSFM is determined and also limited by the thickness of the light sheet and the numerical aperture (NA) of the detection objective. We propose a novel method, light sheet modulation fluorescence microscopy (LSMFM) which is able to achieve a promising axial resolution enhancement of light sheet microscopy.
Nonlinear focal modulation microscopy (NFOMM) is a really simple and effective super-resolution imaging method based on phase modulation with high-intensity illumination, which can extend the effective spatial-frequency bandwidth of the imaging system and achieve a transverse resolution of ~ 60 nm (~λ/10). However, multiple images under different illumination pattern is needed, which result in limited imaging speed. A novel interleaved reconstruction method is proposed to increase the frame rate without any change in the raw data of NFOMM. Since allowing easy integration with confocal microscopes, we anticipate this method will be a useful observation tool in the biological community and other research field.