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.