Physical Sciences and Mathematics Commons^™

Ambient Ionization - Mass Spectrometry: Advances Toward Intrasurgical Cancer Detection, Alan Keith Jarmusch

Open Access Dissertations

My dissertation research has focused on the development of ambient ionization – mass spectrometry (MS) for clinical measurements, specifically intrasurgical cancer detection. The molecular differences between normal and cancerous tissue were detected via direct tissue analysis in vitro by touch spray ionization (TS) or by analyzing sectioned or smeared tissue using desorption electrospray ionization (DESI). The physical form of the tissue, e.g. in vitro sampling, sectioned, or smeared, was inconsequential in differentiating normal from cancerous tissue; however, the spectra acquired by TS and DESI differed due to differences in ionization processes. We envision that TS-MS and DESI-MS could impact diagnostic …

Preparative Mass Spectrometry Applications In Nanomaterials And Organic Synthesis, Michael Wleklinski

Open Access Dissertations

Preparative mass spectrometry was traditionally a vacuum based experiment where mass selected ion beams were deposited onto surfaces; however, recently ions have been manipulated in the open air to perform accelerated synthesis. The work of this dissertation focuses on the generation of charged ions from microdroplets and their use in organic synthesis and the preparation of atomically precise metal nanoclusters. First the mechanism for charging in the zero volt paper spray will be presented. This works builds a computational model based on the statistical fluctuation of positive and negative charges based on the theory of Dodd. It is found through …

Synthesis And Performance Of Novel Supramolecular Tools For Single-Particle Cryogenic Electron Microscopy And Drug And Gene Delivery, Kyle J. Wright

Open Access Dissertations

High-resolution biomacromolecular structure elucidation is fundamentally important to structure-based drug design and basic research into complex biochemical processes. Cryo-EM is an emerging alternative to XRD and NMR that is complementary in many ways relative to XRD and NMR. Materials approaches to cryo-EM are anticipated to greatly facilitate the cryo-EM process, allowing progress toward a more high-throughput application of cryo-EM to address challenges in structural biology. ^ Various affinity-based approaches inspired by approaches previously introduced for 2D crystallization were developed for facilitation of cryo-EM. A library of affinity lipopolymer constructs were synthesized consisting of lipopolymers of various PEG molecular weights conjugated …

In-Column Polymer Modifications: Advancing Polymer Bonded Phases, Alexis G. Huckabee

Open Access Dissertations

Glycosylation is the most common post-translational modification affecting protein activities, including delivery to cell surface, binding affinity, and mediating different physiological effects. Separations of glycoproteins and their glycoforms are essential for drug discovery and development, identification of potential disease biomarkers and quality control. The efficiency of glycoprotein separations is limited by the bonded phases, requiring advances in chromatographic materials. Such advances would improve resolution, allowing for more species to be isolated from a mixture and studied.

Our group found that submicrometer nonporous silica stationary phases with tethered polymer chains (acrylamide) give excellent hydrophilic liquid chromatography (HILIC), a common method used …

Ultraviolet And Infrared Spectroscopy Of Synthetic Foldamers, Aib Homopeptides, And Solvated 1,2-Diphenylethane In The Gas Phase, Joseph R. Gord

Open Access Dissertations

The work presented here implements a supersonic jet expansion source to funnel the population of model peptides and solvated-bichromophore clusters into their low lying structural minima and to collisionally cool these minima to their respective zero-point vibrational levels. Single-conformation ultraviolet and infrared spectroscopy techniques are then used to probe these systems and investigate their electronic properties and uncover their intrinsic conformational preferences in the gas phase.

Model β/γ-peptides known as synthetic foldamers and aminoisobutyric acid (Aib) homopeptides incorporate structural constraints that are designed/known to impose particular structural motifs. Here the ability of a β/γ-dipeptide to replicate the backbone length of …

The Use Of Stable Isotopes And Particulate Matter In The Investigation Of Local And Regional Atmospheric Chemistry, Tanya Lynn Katzman

Open Access Dissertations

The chemical composition of particulate matter (PM), a known contributor to air pollution, is highly variable, and elemental analysis reveals information about local and regional sources, as well as how air masses and climate influence PM compositions. Seasonal changes in climate, such as temperature, amount of daylight, or meteorological patterns influence source emissions (increased residential heating activities, decreased natural soil emissions) and the relative importance of certain chemical pathways in the atmosphere. Since the magnitude of these seasonal changes are highly dependent on location, each sampling site is unique and the chemical composition of PM provides valuable insight into local …

Advances In Raman Hyperspectral Compressive Detection Instrumentation For Fast Label Free Classification, Quantitation And Imaging, Bharat R. Makani

Open Access Dissertations

Multiple prototypes of hyperspectral compressive detection (CD) Raman spectrometers have previously been constructed in the Ben-Amotz lab and have proven to be useful for fast, label-free chemical identification, quantitation and imaging. The CD spectrometer consists of a volume holographic grating (VHG) that linearly disperses the Raman photons into its component wavelengths and all wavelengths are focused onto a digital micromirror devise (DMD). The DMD is an optical modulator that consists of an array of programmable 10μm mirrors that can reflect photons in either +12° or -12° to the incoming light. The DMD is tilted such that the +12° photons go …

Coupling Qualitative And Quantitative Analyses Of Pharmaceutical Materials Enabled By Second Harmonic Generation Microscopy, Paul D. Schmitt

Open Access Dissertations

The detection and characterization of crystallinity is critical throughout the drug development process. From the initial establishment of an active pharmaceutical ingredient’s (API) crystal structure to stability testing and quality control, the phase of an API affects the solubility, bioavailability, stability, and efficacy of a drug product. Second harmonic generation (SHG) microscopy has recently been developed as a selective and rapid method for imaging crystallinity in drug formulations. While SHG microscopy can enable the high signal-to-noise (SNR) detection of crystallinity, the intrinsic chemical information content within SHG images is relatively low. In cases of trace crystallinity and/ or small crystal …

Direct Drug Screening And Lipid Profiling Using Ambient Mass Spectrometry, Yuan Su

Open Access Dissertations

Mass spectrometry (MS) stands in an outstanding position in analysis of biological specimens owing to its abundant structural information, high accuracy, incomparable sensitivity, high speed, and the large variety of its applications. The ion source, an instrumental part for converting the analyte into ions, has played an important role in analyzing biological specimens by MS. However, the performance of conventional spray-based ionization methods always suffers from chemical interferences derived from complex biological matrices. A series of sample extraction, purification, and separation steps is required before the ionization, so as to ensure excellent performance of MS analysis. In order to simplify …

Advances In Solid Phase Microextraction For The Analysis Of Volatile Compounds In Explosives, Tire Treatments, And Entomological Specimens, William D. Kranz

Open Access Dissertations

Solid phase microextraction is a powerful and versatile technique, well-suited to the analysis of numerous samples of forensic interest. The exceptional sensitivity of the SPME platform, combined with its adaptability to traditional GC-MS systems and its ability to extract samples with minimal work-up, make it appropriate to applications in forensic laboratories.

In a series of research projects, solid phase microextraction was employed for the analysis of explosives, commercial tire treatments, and entomological specimens. In the first project, the volatile organic compounds emanating from two brands of pseudo-explosive training aids for use in detector dog imprinting were determined by SPME-GC-MS, and …

Mass Spectrometric Characterization Of Peptide Radical Ions And Implication For Radical Chemistry, Lei Tan

Open Access Dissertations

Gas-phase radical ion chemistry has attracted increasing research interest from the mass spectrometry (MS) society because it provides new capabilities in bio-analysis which often complements traditional MS methods developed from even-electron ions. Fundamental studies of biomolecule related radical species are essential to broadening the scope of radical chemistry and pushing the frontiers of its analytical applications. This dissertation mainly discusses the gas-phase chemistry of peptide sulfinyl radicals (-SO·), which has been rarely studied before. In order to establish an effective research approach, a method that can generate site-specific peptide sulfinyl radical ion has been developed. This method is based on …

Studies Of Arctic Halogen Chemistry From The Snowpack To The Gas Phase, Kyle D Custard

Open Access Dissertations

The temporary depletion of both tropospheric ozone and gaseous mercury during the Arctic springtime has been a focus of active research over the past several decades. Both of these phenomena have been linked to chemical reactions with halogen radicals. In particular, bromine atoms have been shown to act as the primary driver for these chemical depletions, although both chlorine and iodine atoms also contribute. Molecular bromine, along with its oxidation products, have been well studied in the Arctic, yet chlorine has not. Chlorine is known to impact the local oxidation capacity via its high reactivity with volatile organic compounds. Despite …

Polarization-Dependent Nonlinear Optical Microscopy Methods For The Analysis Of Crystals And Biological Tissues, Emma L. Kerian

Open Access Dissertations

The ability to solve a high-resolution protein structure is largely dependent on the successful generation and identification of protein crystals prior to X-ray diffraction (XRD). For novel protein targets, high-throughput crystallography often involves generation of multiple targets and thousands of crystallization trials per target to generate diffraction-quality crystals. Second harmonic generation (SHG) imaging has been developed as a fast, non-destructive and sensitive method for the selective identification of protein crystals, even in highly scattering environments. Polarization-dependent SHG microscopy methods were developed to assess the presence of multidomain crystals to provide a handle on crystal quality. In addition, polarization-dependent two-photon excited …

Development Of Experimental And Instrumental Systems To Study Biological Systems, Amanda J Hemphill

Open Access Dissertations

Chapters 1-4 of this thesis describes the development of an experimental system to measure diffusion-limited reaction kinetics in a biological environment. About 100 years ago, the relationship between reaction rate and diffusion in homogenous solution, ie water or buffer, was described as a linear relationship by Smoluchowski. Applying this theory naively would suggest that since the diffusion coefficients drop by factors of 4-100 then the rates of reaction would drop by the same amount. However, recent theory and simulations suggest that this does not hold. Even though biological diffusion coefficients drop to 0.1-20% of that in buffer, these recent studies …

Molecular Diagnosis Of Cancer Using Ambient Ionization Mass Spectrometry, Kevin S Kerian

Open Access Dissertations

My dissertation focuses on advancing the development and application of ambient ionization mass spectrometry methodology and technology to the biomedical field. The primary ambient ionization method used in my studies is desorption electrospray ionization mass spectrometry (DESI-MS) imaging, which has been previously used to analyze and differentiate disease state (i.e. tumor and normal) and in some cases tumor subtype of human liver, kidney, bladder, testicular, prostate, and brain cancers. DESI-MS imaging is an ideal method for disease diagnosis, because it can be used to directly correlate disease state with histopathology to develop and validate MS libraries built using the molecular …

Laboratory Studies On The Production Of Alpha-Pinene-Derived Organic Nitrates And Their Atmospheric Fate, Joel David Rindelaub

Open Access Dissertations

Currently, the formation yields of organic nitrates from the oxidation of biogenic volatile organic compounds, such as α-pinene, is highly uncertain, negatively impacting our knowledge on tropospheric ozone production and the fate of atmospheric NO_x. To lower this uncertainty, we quantified the organic nitrate yield from the OH radical oxidation of α-pinene under high NO_x conditions. The α-pinene- derived nitrates created in chamber experiments readily partitioned to the aerosol phase and underwent particle phase hydrolysis, indicating that these processes are likely a sink for atmospheric NO_x. The hydrolysis of organic nitrates was found to be …

Structure-Activity Relationships For The Water-Gas Shift Reaction Over Supported Metal Catalysts, Kaiwalya D. Sabnis

Open Access Dissertations

The Water-Gas Shift (WGS) reaction (CO + H₂O → CO₂ + H₂) is an important chemical process for industrial hydrogen production. The overall goal of this project is to use kinetic experiments and in situ characterization techniques in tandem, in order to derive structure-activity relationships for various catalytic systems. These relationships facilitate the rational catalyst design by identification of catalyst descriptors. In order to establish such relationships, various studies were undertaken, such as (i) effect of transition admetals on the WGS catalysis by molybdenum carbide (ii) effect of residual oxygen content on the performance of …

Aircraft-Based Measurements For The Identification And Quantification Of Sources And Sinks In The Carbon Cycle, Dana R Caulton

Open Access Dissertations

Improved quantification of carbon-cycle sources and sinks is an important requirement for determining mitigation strategies and modeling future climate interactions. Analytically robust measurements require high-precision instrumentation and thoughtful experimental design to produce rigorous and reproducible results despite complex and quickly changing meteorological and environmental conditions. Here, an aircraft platform equipped with a high-precision cavity ring-down spectrometer for CO₂, CH₄ and H₂O quantification was used to acquire data from previously un-sampled sources. The aircraft mass-balance technique was used to quantify CH4 emissions from natural gas well pads in the drilling stage, which were 2-3 orders of …

Metal-Protein Interactions For Proteomics Applications, Keerthi B Jayasundera

Open Access Dissertations

In the quest of deciphering biological mechanisms, the understanding of proteins and their functions is a vital component. However the complexity of the proteome poses an immense challenge for analytical chemists to explore it comprehensively. Currently mass spectrometry is at the forefront of proteome analysis, providing great capabilities to couple with modern separation techniques for wide applications. One major objective of current proteomic technologies is to identify proteins of interest among high background, in particular from complex biological samples. A variety of techniques have been developed over the years to simplify protein samples, which are broadly classified as enrichment, high …

Reactivity Studies Of Tridhydropyridine Radical Cautions By Using Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry And Advancement Of Mass Spectrometric Analysis Of Asphaltenes And Degradation Products, Mohammad Sabir Aqueel

Open Access Dissertations

Aromatic organic molecules which have unpaired electrons play an important role in a variety of applications in the fields of organic synthesis, organic magnets, and biological activity of organic compounds. Several studies have been published on σ- type carbon-centered mono- and biradicals. Reactive intermediates with three formally unpaired electrons are known as triradicals. They can be defined as species with three electrons distributed in three degenerate or nearly degenerate orbitals, based on Salem's definition of biradicals from the electronic structure point of view. Very little is known about the reactivity of carbon-centered σ,σ,σ- triradicals due to the complexity of studying …

Construction And Demonstration Of A Tandem Mass Spectrometer Based Instrument For Cold Ion Spectroscopy, James Gerhardt Redwine

Open Access Dissertations

A new instrument incorporating ion trap based tandem mass spectrometry and cold ion UV and UV-IR double resonance spectroscopy has been developed at Purdue University for the study of gas phase, biologically relevant ions. The instrument incorporates multiple quadrupole linear ion trap mass analyzers to prepare and isolate the precursor ions as well as to analyze the resultant photofragments. A 22-pole ion trap cooled to 5 K via a closed cycle helium cryostat is used to cool the ions for spectroscopic interrogation. Results show the vibrational and rotational temperature of a wide assortment of ions to be 12±2 K.

The …

Instrumentation, Applications And Fundamentals Of Plasma Ionization Of Organic Molecules From Surfaces, Joshua Scott Wiley

Open Access Dissertations

Various aspects of the interaction of low-temperature plasma (LTP) ambient ionization with organic molecules and surfaces are discussed. As an application, LTP-MS has been used for the analysis of pesticides directly from fruits and vegetables revealing low parts per billion limits of detection (LODs). Due to low power and gas requirements, a battery-operated and handheld LTP probe was developed for the point-and-shoot MS analyses. Handheld LTP was compared with large-scale LTP on a benchtop and miniature MS revealing similar LODs for both. Long-distance ion transport up to one meter was also demonstrated with flexible tubing for non-proximate sample interrogation. Fundamentals …

Development Of Quantitative Ft- Ir Methods For Analyzing The Cure Kinetics Of Epoxy Resins, Sang Ha Son

Open Access Dissertations

Epoxy thermosets are important engineering materials with applications in coating, adhesives, packaging and as structural components in a variety of advanced engineering products. The ultimate performance of polymer critically depends upon the details of the cure chemistry used to produce the thermoset. In order to better understand and monitor the cure chemistry, quantitative analysis of the FT-IR response has been developed for describing the epoxy-amine curing reaction as well as monitoring the hydrogen bonding that occurs in these systems The FT-IR analysis includes (i) quantitative deconvolution of complex peaks into individual spectral contributions, (ii) peak identification via DFT analysis and …

Development Of Isotags For Nmr Based Metabolite Profiling And Applications, Fariba Tayyari

Open Access Dissertations

NMR spectroscopy is a powerful analytical tool for both qualitative and quantitative metabolite profiling analysis. However, accurate quantitative analysis of biological systems especially using one dimensional NMR has been challenging due to signal overlap. In contrast, the enhanced resolution and sensitivity offered by chemoselective isotope tags have enabled new and enhanced methods for detecting hundreds of quantifiable metabolites in biofluids using NMR spectroscopy or mass spectrometry. In this thesis we show improved sensitivity and resolution of NMR experiments imparted by 15N and 13C isotope tagging which enables the accurate analysis of plasma metabolites. To date, isotope tagging has been used …

Silica Colloidal Crystals As Emerging Materials For The High-Throughput Sizing Of Proteins By Packed Capillary Electrophoresis, Nadine K. Njoya

Open Access Dissertations

Protein heterogeneity is currently one of the leading problems in formulation of therapeutic proteins. The effectiveness of therapeutic proteins is diminished when they exhibit heterogeneity due to aggregates and degradation by-products. Furthermore, guidelines set forth by the FDA require therapeutic proteins to have high stability as well as high purity. With development time on the order of years and costs incurred in the millions, pharmaceutical companies are investing more time in finding fast and efficient ways to screen for protein heterogeneity. Current methods such as native polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC) and capillary electrophoresis (CE) are time consuming, …

Utilizing Electron Microscopy And Spectroscopy Methods To Understand Water Structure And Water Doping, Lior Miller

Open Access Dissertations

Water is the second most common element in the universe and the most studied material on earth. Most of the studies concerning water are from the fields of chemistry and biology. Hence, the structure of water molecules and short range order and interactions are well characterized and understood. However, the collective arrangement of water molecules and the long range order are still missing. Understanding of this long range order in water is needed, as it is the key to many water activities.

To fill this gap, this study utilizes a new direct method for characterization of water in the vapor …

Spectroscopic Characterization Of The Water-Oxidation Intermediates In The Ru-Based Catalysts For Artificial Photosynthesis, Dooshaye Moonshiram

Open Access Dissertations

Utilization of sunlight requires solar capture, light-to-energy conversion and storage. One effective way to store energy is to convert it into chemical energy by fuel-forming reactions, such as water splitting into hydrogen and oxygen. Ruthenium complexes are among few molecular-defined catalysts capable of water splitting. Insight into the mechanism of their action will help to design future robust and economically feasible catalysts for light-to-energy conversion. Mechanistic insights about the design of such catalysts can be acquired through spectroscopic analysis of short-lived intermediates of catalytic water oxidation. Development of time-resolved approaches through stopped flow UV-Vis Spectroscopy to follow the catalysis of …

Top-Down Interrogation And Characterization Of Biological Macromolecules, Yang Gao

Open Access Dissertations

Analytical mass spectrometry has been widely applied in the field of biomolecule identification and characterization. It provides fast, accurate and robust information relevant to the molecular mass, composition and structure of the target analytes.

This thesis is focused on the top-down analysis of various macrobiomolecules, nucleic acids and proteins, in the context of ion/ion reaction and gas-phase unimolecular dissociation. The first part of the thesis deals with gas phase fragmentation behavior of chemically modified oligonucleotides. Factors, such as the observation time-scale, the ion type and the energy deposition method, are explored using a quadrupole/time-of-flight mass spectrometer. Novel fragmentation pathway associated …

Mass Spectrometric Studies On The Primary Products Of Fast Pyrolysis Of Carbohydrates And The Molecular Structures Of Asphaltenes, And The Development Of A Rastering Probe For Laser-Induced Acoustic Desorption Into An Atmospheric Pressure Chemical Ionization Source, Matthew Robert Hurt

Open Access Dissertations

Mass spectrometry (MS) has proven invaluable in the field of mixture analysis and structural elucidation. Tandem mass spectrometry (MS/MS) utilizing collision-activated dissociation (CAD) has become the technique of choice for structural elucidation of unknown analytes in mixtures. When coupled with gas chromatography (GC) or high performance liquid chromatography (HPLC), it allows for trace level analysis of mixture components. In spite of the utility of mass spectrometry in complex mixture analysis, it does have limitations. Traditional GC/MS methods used for the analysis of fast pyrolysis products cannot be used to analyze the primary products, thus limiting the knowledge that can be …

Structural Analysis Of Carbohydrates By Mass Spectrometry, Chiharu Konda

Open Access Dissertations

Protein glycosylation is a highly frequent post-translational modification. Glycosylation is actively involved in intermolecular and intercellular binding events that are important to a wide range of biological functions such as immunity and fertility. The unique functions of glycans are directly related to their structures. In order to fully characterize the structure of an unknown glycan, 5 levels of structural information is needed: sugar unit identity, anomeric configuration, linkage types, sequence, and branching location. One of the grand challenges limiting the advance of glycosciences is the lack of sensitive tools for detailed glycan structural analysis. Tandem mass spectrometry (MS/MS) is a …