In conventional light-sheet microscopy, a sample is illuminated by a thin layer of light perpendicular to the detection axis. This reduces the background illumination and improves single-molecule localization. However, these configurations come with certain drawbacks and are often complex and expensive. Gustavsson et al. present an easier and cheaper method to achieve super-resolution with a light-sheet microscope. They found that when they tilted the illumination plane, they could image cells all the way down to the coverslip. Only one objective is needed for this approach, which allows the use of a high-numerical-aperture objective. In combination with 3D point-spread functions, this system achieves localization precision to tens of nanometers without losing the advantages of light-sheet microscopy.
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Tilted light-sheet microscopy with 3D point-spread functions. Nat Methods 15, 163 (2018). https://doi.org/10.1038/nmeth.4614