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Sample Preparation Strategies for High-Throughput Mass Spectrometry Imaging of Primary Tumor Organoids

Authors
  • Johnson, Jillian1
  • Sharick, Joe T.2
  • Skala, Melissa C.2, 3
  • Li, Lingjun1, 4
  • 1 School of Pharmacy, University of Wisconsin-Madison, Madison, WI, USA
  • 2 Morgridge Institute for Research, Madison, WI, USA
  • 3 Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
  • 4 Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA
Type
Published Article
Journal
Organic Mass Spectrometry
Publisher
Wiley (John Wiley & Sons)
Publication Date
Jan 21, 2020
Volume
55
Issue
4
Identifiers
DOI: 10.1002/jms.4452
PMID: 31661714
PMCID: PMC7254934
Source
PubMed Central
Keywords
License
Unknown

Abstract

Patient-derived 3D organoids show great promise for understanding patient heterogeneity and chemotherapy response in human-derived tissue. The combination of organoid culture techniques with mass spectrometry imaging provide a label-free methodology for characterizing drug penetration, patient-specific response, and drug biotransformation. However, current methods used to grow tumor organoids employ extracellular matrices which can produce small molecule background signal during mass spectrometry imaging analysis. Here, we develop a method to isolate 3D human tumor organoids out of a Matrigel extracellular matrix into gelatin mass spectrometry compatible microarrays for high-throughput MS imaging analysis. The alignment of multiple organoids in the same z-axis is essential for sectioning organoids together and for maintaining reproducible sample preparation on a single glass slide for up to hundreds of organoids. This method successfully removes organoids from extracellular matrix interference and provides an organized array for high-throughput imaging analysis to easily identify organoids by eye for area selection and further analysis. With this method, mass spectrometry imaging can be readily applied to organoid systems for pre-clinical drug development and personalized medicine research initiatives.

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