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Development of Advanced Optics and High Resolution Instrumentation for Mass Spectrometry Based Proteomics

Imaging mass spectrometry (MS) analysis allows scientists the ability to obtain
spatial and chemical information of analytes on a wide variety of surfaces. The ability to
image biological analytes is an important tool in many areas of life science research,
including: the ability to map pharmaceutical drugs in targeted tissue, to spatially
determine the expression profile of specific proteins in healthy vs. diseased tissue states,
and to rapidly interrogate biomolecular microarrays. However, there are several avenues
for improving the imaging MS experiment for biological samples. Three significant
directions this work addresses include: (1) reducing chemical noise and increasing
analyte identification by developing sample preparation methodologies, (2) improving
the analytical figures of merit (i.e., spatial resolution, analysis time) by implementing a
spatially dynamic optical system, and (3) increasing both mass spectral resolution and
ion detection sensitivity by modifying a commercial time-of-flight (TOF) MS.
Firstly, sample methodology schemes presented in these studies consist of
obtaining both ?top-down? and ?bottom-up? information. In that, both intact mass and
peptide mass fingerprinting data can be obtained to increase protein identification. This sample methodology was optimized on protein microarrays in preparation for bio tissue
analysis. Other work consists of optimizing novel sample preparation strategies for
hydrated solid-supported lipid bilayer studies. Sample methods incorporating
nanomaterials for laser desorption/ionization illustrate the ability to perform selective
ionization of specific analytes. Specifically, our results suggest that silver nanoparticles
facilitate the selective ionization of olefin containing species (e.g., steroids, vitamins).
Secondly, an advanced optical design incorporating a spatially dynamic optical
scheme allows for laser beam expansion, homogenization, collimation, shaping, and
imaging. This spatially dynamic optical system allows user defined beam shapes,
decreases analysis times associated with mechanical movement of the sample stage, and
is capable of increasing the MS limits of detection by simultaneously irradiating multiple
spots.
Lastly, new data acquisition strategies (multiple anode detection schemes) were
incorporated into a commercial time-of-flight mass spectrometer to increase both
sensitivity and resolution in a matrix assisted laser desorption/ionization mass
spectrometer. The utility of this technique can be applied to many different samples,
where high mass spectral resolution allows for increased mass measurement accuracy.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2008-12-192
Date14 January 2010
CreatorsSherrod, Stacy D.
ContributorsRussell, David H.
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
TypeBook, Thesis, Electronic Dissertation
Formatapplication/pdf

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