posted on 2021-02-19, 21:13authored byNicole Strittmatter, Richard M. England, Alan M. Race, Daniel Sutton, Jennifer I. Moss, Gareth Maglennon, Stephanie Ling, Edmond Wong, Jonathan Rose, Ian Purvis, Ruth Macdonald, Simon T. Barry, Marianne B. Ashford, Richard J. A. Goodwin
Imaging
mass cytometry (IMC) offers the opportunity to image metal-
and heavy halogen-containing xenobiotics in a highly multiplexed experiment
with other immunochemistry-based reagents to distinguish uptake into
different tissue structures or cell types. However, in practice, many
xenobiotics are not amenable to this analysis, as any compound which
is not bound to the tissue matrix will delocalize during aqueous sample-processing
steps required for IMC analysis. Here, we present a strategy to perform
IMC experiments on a water-soluble polysarcosine-modified dendrimer
drug-delivery system (S-Dends). This strategy involves two consecutive
imaging acquisitions on the same tissue section using the same instrumental
platform, an initial laser ablation inductively coupled plasma mass
spectrometry (LA-ICP-MSI) experiment followed by tissue staining and
a standard IMC experiment. We demonstrated that settings can be found
for the initial ablation step that leave sufficient residual tissue
for subsequent antibody staining and visualization. This workflow
results in lateral resolution for the S-Dends of 2 μm followed
by imaging of metal-tagged antibodies at 1 μm.