In situ X-ray assisted electron microscopy staining for large biological samples
Authors: Sebastian Ströh, Eric W. Hammerschmith, David W. Tank, H. Sebastian Seung, Adrian A. Wanner
publication: bioRxiv 2021
Electron microscopy of biological tissue has recently seen an unprecedented increase in imaging throughput moving the ultrastructural analysis of large tissue blocks such as whole brains into the realm of the feasible. However, homogeneous, high quality electron microscopy staining of large biological samples is still a major challenge. To date, assessing the staining quality in electron microscopy requires running a sample through the entire staining protocol end-to-end, which can take weeks or even months for large samples, rendering protocol optimization for such samples to be inefficient. Here we present an in situ time-lapsed X-ray assisted staining procedure that opens the "black box" of electron microscopy staining and allows observation of individual staining steps in real time.