Super-resolution fluorescence microscopy for imaging in thick samples would benefit greatly from a reduction in fluorescence background and an increase in acquisition speed. To address these concerns, we present a single-objective tilted light sheet combined with four additional innovations: (i) a 3D-printed microfluidic chip, (ii) sequential DNA Point Accumulation for Imaging in Nanoscale Topography (DNA-PAINT) known as Exchange-PAINT, (iii) deep learning for improved localization precision and imaging speeds, and (iv) engineered point spread functions for 3D imaging. Our approach achieves improved localization precision, imaging speeds, and multi-target accuracy, enabling fast and precise multi-target 3D super-resolution imaging.
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