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Differential interference contrast (DIC) microscopy allows high-contrast, low-phototoxicity, and label-free imaging of transparent biological objects, and has been applied in the field of cellular morphology, cell segmentation, particle tracking, optical measurement and others. Commercial DIC microscopy based on Nomarski or Wollaston prism resorts to the interference of two polarized waves with a lateral differential offset (shear) and axial phase shift (bias). However, the shear generated by these prisms is limited to the rectilinear direction, unfortunately resulting in anisotropic contrast imaging. Here we propose an ultracompact metasurface-assisted isotropic DIC (i-DIC) microscopy based on a grand original pattern of radial shear interferometry, that converts the rectilinear shear into rotationally symmetric along radial direction, enabling single-shot isotropic imaging capabilities. The i-DIC presents a complementary fusion of typical meta-optics, traditional microscopes and integrated optical system, and showcases the promising and synergetic advancements in edge detection, particle motion tracking, and label-free cellular imaging.

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Super-resolution (SR) imaging with high-throughput is invaluable to fast and highprecision profiling in a wide range of biomedical applications. However, prevalent SR methods require sophisticated acquisition devices and specific imaging control, and may cost a fairly long time on a single field-of-view. These essentially increase the construction difficulty, including challenges in imaging throughput, system establishment, and automation. Using the natural photophysics of fluorescence, fluctuation-based microscopy techniques can routinely break the diffraction limit with no need for additional optical components, but its long acquisition time still poses a challenge for high-throughput imaging or visualizing transient organelle dynamics. Here, we propose an SR method based on the Auto-Correlation with two-step Deconvolution (SACD) that reduces the number of frames required by maximizing the detectable fluorescence fluctuation behavior in each measurement, with further removal of tunable parameters by a Fourier ring correlation analysis. It only needs 20 frames for twofold lateral and axial resolution improvements, while the SR optical fluctuation imaging (SOFI) needs more than 1000 frames. By capturing raw images for ~10 minutes, we record an SR image with ~128 nm resolution that contains 2.4 gigapixels covering an area of ~2.0 mm × 1.4 mm, including more than 2,000 cells. Beyond that, by applying continuity and sparsity joint constraint, the Sparse deconvolution-assisted SACD enables 4D live-cell SR imaging of events such as mitochondrial fission and fusion. Overall, as an open-sourced module, we anticipate SACD can offer direct access to SR, which may facilitate the biology studies of cells and organisms with high-throughput and low-cost.In quantitative biology, the microscopy-based high-throughput screening is used to monitor the variability of biological systems as well as examine the heterogeneity 1 , and the advances in three-dimensional (3D) resolution can contribute to the minimization of the uncertainties in analyzing noisy biological processes. In parallel, super-resolution (SR) microscopy techniques relying on the blinking of single fluorophores have been developed to break the diffraction limit, including photoactivated localization microscopy (PALM) 2 and stochastic optical reconstruction microscopy (STORM) 3 . However, precisely localizing individual fluorophores requires tens of thousands of frames to accumulate one final SR view, which inherently limits the throughput and leads to requirements for purpose-built experimental settings 4 . Therefore, although livecell PALM/STORM has been reported 5-7 , excessive illumination power (~10 kW/cm 2 ) 8 , long exposures (>2 s) 9 , and the particular photochemical environment that promotes long dark states to reduce bleaching 9 prevent it from being a general live-cell imaging method 10 with high-throughput.