posted on 2021-05-27, 00:17authored byHua Tian, Sadia Sheraz née Rabbani, John C. Vickerman, Nicholas Winograd
Integration of multiomics
at the single-cell level allows the unambiguous
dissecting of phenotypic heterogeneity at different states such as
health, disease, and biomedical response. Imaging mass spectrometry
holds the promise of being able to measure multiple types of biomolecules
in parallel in the same cell. We have explored the possibility of
using water gas cluster ion beam secondary ion mass spectrometry [(H2O)n-GCIB-SIMS] as an analytical
tool for multiomics assay. (H2O)n-GCIB has been hailed as an ideal ionization source for biological
sampling owing to the enhanced chemical sensitivity and reduced matrix
effect. Taking advantage of 1 μm spatial resolution by using
a high-energy beam system, we have clearly shown the enhancement of
multiple intact biomolecules up to a few hundredfold in single cells.
Coupled with the cryogenic sample preparation/measurement, the lipids
and metabolites were imaged simultaneously within the cellular region,
uncovering the pristine chemistry for integrated omics in the same
sample. We have demonstrated that double-charged myelin protein fragments
and single-charged multiple lipids and metabolites can be localized
in the same cells/tissue with a single acquisition. Our exploration
has also been extended to the capability of (H2O)n-GCIB in the generation of multiple charged peptides
on protein standards. Frozen hydration combined with (H2O)n-GCIB provides the possibility of
universal enhancement for the ionization of multiple bio-molecules,
including peptides/proteins which has allowed “omics”
to become feasible in the same sample using SIMS.