High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry

Yin, Ruichuan; Burnum-Johnson, Kristin E.; Sun, Xiaofei; Dey, Sudhansu K.; Laskin, Julia

doi:10.1038/s41596-019-0237-4

High spatial resolution imaging of biological tissues using nanospray desorption electrospray ionization mass spectrometry

Journal Article · Wed Nov 13 00:00:00 EST 2019 · Nature Protocols

DOI:https://doi.org/10.1038/s41596-019-0237-4· OSTI ID:1608770

^[1]; ^[2]; ^[3]; Dey, Sudhansu K. ^[3]; ^[4]

Purdue Univ., West Lafayette, IN (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Univ. of Cincinnati, OH (United States)
Purdue Univ., West Lafayette, IN (United States); Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Mass spectrometry imaging (MSI) enables label-free spatial mapping of hundreds of biomolecules in tissue sections. This capability provides valuable information on tissue heterogeneity that is difficult to obtain using population-averaged assays. Despite substantial developments in both instrumentation and methodology, MSI of tissue samples at single-cell resolution remains challenging. In our research, we describe a protocol for robust imaging of tissue sections with a high (better than 10-μm) spatial resolution using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry, an ambient ionization technique that does not require sample pretreatment before analysis. In this protocol, mouse uterine tissue is used as a model system to illustrate both the workflow and data obtained in these experiments. We provide a detailed description of the nano-DESI MSI platform, fabrication of the nano-DESI and shear force probes, shear force microscopy experiments, spectral acquisition, and data processing. A properly trained researcher (e.g., technician, graduate student, or postdoc) can complete all the steps from probe fabrication to data acquisition and processing within a single day. We further describe a new strategy for acquiring both positive- and negative-mode imaging data in the same experiment. This is achieved by alternating between positive and negative data acquisition modes during consecutive line scans. Using our imaging approach, hundreds of high-quality ion images were obtained from a single uterine section. This protocol enables sensitive and quantitative imaging of lipids and metabolites in heterogeneous tissue sections with high spatial resolution, which is critical to understanding biochemical processes occurring in biological tissues.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1608770

Report Number(s):: PNNL-SA--142602

Journal Information:: Nature Protocols, Journal Name: Nature Protocols Journal Issue: 12 Vol. 14; ISSN 1754-2189

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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