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Disease Tissue Imaging and Single Cell Analysis with Mass Spectrometry

Cells have been found to have an inherent heterogeneity that has led to an increase in the development of single-cell analysis methods to characterize the extent of heterogeneity that can be found in seemingly identical cells. With an understanding of normal cellular variability, the identification of disease induced cellular changes, known as biomarkers, may become more apparent and readily detectable. Biomarker discovery in single-cells is challenging and needs to focus on molecules that are abundant in cells. Lipids are widely abundant in cells and play active roles in cellular signaling, energy metabolism, and are the main component of cellular membranes. The regulation of lipid metabolism is often disrupted or lost during disease progression, especially in cancer, making them ideal candidates as biomarkers. Challenges exist in the analysis of lipids beyond those of single-cell analysis. Lipid extraction solvents must be compatible with the lipid or lipids of interest. Many lipids are isobaric making mass spectrometry analysis difficult without separations. Single-cell extractions using nanomanipulation coupled to mass spectrometry has shown to be an excellent method for lipid analysis of tissues and cell cultures. Extraction solvents are tunable for specific lipid classes, nanomanipulation prevents damage to neighboring cells, and lipid separations are possible through phase dispersion. The most important aspect of single-cell analysis is that it uncovers the extent of cellular heterogeneity that exists among cellular populations that remains undetected during averaged sampling.

Identiferoai:union.ndltd.org:unt.edu/info:ark/67531/metadc984137
Date05 1900
CreatorsHamilton, Jason S.
ContributorsVerbeck, Guido F., Chapman, Kent Dean, Golden, Teresa Diane, 1963-, Wang, Hong
PublisherUniversity of North Texas
Source SetsUniversity of North Texas
LanguageEnglish
Detected LanguageEnglish
TypeThesis or Dissertation
Formatviii, 121 pages, Text
RightsPublic, Hamilton, Jason S., Copyright, Copyright is held by the author, unless otherwise noted. All rights Reserved.

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