3.6 Expansion microscopy
Expansion microscopy is an unusual SRN approach that uses the physical expansion of a sample by synthesising a swellable polymer network inside it (Figure 2f) (Chen et al., 2015). Imaging of such expanded samples alleviates some of the limitations of conventional microscopes and leads to lateral and axial resolution improvement to several tens of nanometres. Expansion microscopy has been used to map the molecular organisation of the lateral hypothalamus in mice (Wang et al., 2021) and accurately detect melatonin receptor 1 localisation in the outer membrane of the brain mitochondria (Suofu et al., 2017). An intriguing recent study combined expansion microscopy with SRRF to achieve a dramatic increase in lateral resolution below 10 nm (Shaib et al., 2023). Although expansion microscopy is in principle incompatible with living samples, its reliance on non-optical methodology for the achievement of resolution enhancement may be beneficial for the study of dense samples with high expression of the labelled molecules or potentially even as a structural biology technique.