Despite super-resolution fluorescence blinking microscopes break the diffraction limit, the intense phototoxic illumination and long-term image sequences thus far still pose to major challenges in visualizing live-organisms. Here, we proposed a super-resolution method based on auto-correlation two-step deconvolution (SACD) to enhance the temporal resolution at lower signal intensity levels. Unlike conventional techniques, such as super-resolution optical fluctuation imaging (SOFI) or stochastic optical reconstruction microscopy (STORM), our model allows 16 frames to generate super-resolution images, without noticeable degradation in recording quality. We demonstrate SACD both in simulated predictions and experimental validations, with the resulting spatial resolution of 64 nm and 2-10 fold speed improvements. The use of low signal-to-noise ratio acquisition of image sequences, our SACD enables fast, background-free, super-resolution imaging that maybe advance implemented as a suitable tool for rapid live-cells imaging.
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