Dissertation/Thesis Abstract

Direct Analysis and Imaging of Biological Tissues by LAESI and NAPA-LDI Mass Spectrometry
by Fincher, Jarod Ashton, Ph.D., The George Washington University, 2019, 209; 13898616
Abstract (Summary)

The emergence of mass spectrometry imaging (MSI) into fields, such as medical diagnostics and the pharmaceutical industry, serves as a testament to its powerful analytical capabilities. The widespread adoption of MSI can be attributed to its ability to detect a broad range of biomolecules, such as proteins, peptides, lipids, and metabolites, while simultaneously mapping out their spatial distributions. As a result, the utility of MSI is now being used to advance the field of histology by helping differentiate between cancerous and noncancerous tissue, which can oftentimes be ambiguous when using traditional histological staining methods. Matrix-assisted laser desorption ionization (MALDI), which offers unparalleled molecular coverage capabilities, has established itself as the method-of-choice for MSI applications. However, challenges still exist with respect to MALDI-MSI, such as the required deposition of a UV-absorbing matrix onto the tissue and the observed ion suppression of neutral lipids, such as triglycerides (TGs), by phospholipids like phosphatidylcholines (PCs). The work presented here describes efforts to advance the field of MSI by mitigating some of these issues.

Chapter 1 introduces the field of MSI with an emphasis on method development, biological applications, and fundamentals of operation for current MSI applications. Chapter 1 addresses how electromagnetic radiation interacts differently with nanomaterials, as opposed to bulk materials.

Chapter 2 demonstrates the advantage of implementing computer-aided design (CAD) software integrated with computational fluid dynamics (CFD) to greatly enhance the sensitivity and transport efficiency in remote laser ablation electrospray ionization (LAESI) mass spectrometry. Using 3-D printers, rapid prototyping of CAD designed remote ablation chambers is possible and greatly reduces time for optimization studies.

Chapter 3 presents silicon nanopost arrays (NAPA) as an MSI platform complementary to MALDI, the current method-of-choice. By comparison of the detected lipid compositions in mouse brain tissue sections, laser desorption ionization (LDI) from NAPA was found to offer enhanced ionization of certain lipid classes, such as phosphatidylethanolamines (PEs) and hexosylceramides (HexCers).

Chapter 4 demonstrates the ability of NAPA to selectively ionize neutral lipids, such as triglycerides (TGs), in the presence of glycerophospholipids, such as phosphatidylcholines (PCs). Historically, the ability to detect TGs from biological tissue sections and cellular lipid extracts by MALDI has remained a significant challenge due to the ion suppression of TGs by PCs.

Chapter 5 demonstrates the potential of NAPA as an MSI platform to map differences in the lipid compositions of diseased human skin tissue with increased bacterial loads. The diseased tissue investigated, Hidradenitis suppurativa (HS), is a potentially debilitating skin disease characterized by chronic inflammation and sinus tract formation. Scanning electron microscopy (SEM) was used to confirm presence of bacteria localized to the hair follicle region.

Chapter 6 summarizes the work presented in this dissertation and addresses possible future directions for remote LAESI and LDI from NAPA. Additionally, the current challenges facing MSI are addressed with respect to its acceptance as a clinical diagnostic tool.

Indexing (document details)
Advisor: Vertes, Akos
Commitee: Miller, Houston, Rodriguez, Erik, Dowd, Cindy, Nemes, Peter
School: The George Washington University
Department: Chemistry
School Location: United States -- District of Columbia
Source: DAI-B 81/2(E), Dissertation Abstracts International
Subjects: Analytical chemistry
Keywords: Mass spectrometry imaging, Matrix-assisted laser desorption ionization, Triglycerides
Publication Number: 13898616
ISBN: 9781085735148
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