We have developed and applied and implementations of structured illumination microscopy (SIM) that offer advantages for live, thick specimens such as worm embryos – ‘instant’ structured illumination microscopy (iSIM2). iSIM enables much more rapid imaging (10-100x improvement) than conventional SIM because only a single image is recorded and most of the image processing occurs during image formation (so less digital post-processing is needed). Additionally, and importantly for nematode embryos, a pinhole array is used to block out-of-focus fluorescence, improving SNR and SBR in these thick, densely labeled samples. iSIM has been commercialized by Visitech International, but if you’d like to build your own, see Curd, A. et al. Construction of an instant structured illumination microscope.