Site‐specific labeling of Affimers for DNA‐PAINT microscopy

Optical super‐resolution techniques allow fluorescence imaging below the classical diffraction limit of light. From a technology standpoint of view, recent methods are approaching molecular‐scale spatial resolution. However, this remarkable achievement is not easily translated to imaging of cellular components, as current labeling approaches are limited by either large label sizes (antibodies) or the sparse availability of small and efficient binders (nanobodies, aptamers, genetically‐encoded tags). Here, we combine recently developed Affimer reagents with site‐specific DNA modification for high‐efficiency labeling and imaging using DNA‐PAINT. We assay our approach using an actin Affimer. The small DNA‐conjugated affinity binders could provide a solution for efficient multi‐target super‐resolution imaging in the future.