Patricia Mabrouk, Geoffrey Davies, Thomas Gilbert
Date of Award
Doctor of Philosophy
Department or Academic Unit
Department of Chemistry and Chemical Biology
chemistry, analytical chemistry, analytical separations, differential mobility spectrometry, forensic science, mass spectrometry, rapid quantitation
Analytical Chemistry | Chemistry
Differential Mobility Spectrometry (DMS) has been interfaced to nano-ESI-MS to conduct rapid separation of ions in the gas phase prior to mass analysis. DMS allows an analyst to simplify a population of electrosprayed ions created from complex mixtures and selectively introduce ions of interest into a Mass Spectrometer (MS) for characterization. The determination of appropriate compensation voltages for targeted analytes by scanning as a function of time is a critical step to isolating species of interest in a rapid fashion. The integration and optimization of DMS separation followed by MS analysis resulted in the development of two DMS-MS prototypes utilized throughout the course of the research studies presented here. These systems have been shown to be efficient at the rapid separation of ions under ambient conditions and have been utilized in our laboratories prior to mass analysis for a number of applications presented herein.
Having established the importance of interfacing DMS to MS in Chapter 1, Chapter 2 details the development and optimization of robust DMS separation methods for the rapid analysis of a wide array of analytes of interest. An in-depth investigation of voltage and temperature effects was conducted followed by a detailed exploration of the effects of transport gas modifiers in the overall separation process. Modifier effects were examined in both a temperature and concentration-dependent fashion in an effort to gain a better understanding of the significant effects that modifiers have in the overall separation process.
Chapter 3 continues the theme of this work by evaluating the abilities of the DMS-MS platforms to accomplish rapid ion separations in the absence of lengthy chromatographic separations for drug of abuse, adulterants and diluents. Forensic laboratories are inundated with thousands of samples requiring lengthy chromatographic separations prior to mass spectrometric characterization. The aim of this work has been the development of a new analytical platform of interest to the forensic science community with the overall goal of developing rapid, quantitative techniques in an effort to address an urgent need to reduce case backlogs at crime laboratories nationwide. Compared to traditional GC-MS and LC-MS methodologies requiring 15 to 45 minutes of chromatography, the presented data demonstrates that mixtures of drugs of abuse, adulterants and diluents could be separated in under one minute of analysis by DMS-MS methods.
Chapter 4 of this work follows the results presented within Chapter 3 for drugs of abuse by developing tandem DMS separation and MS quantitative analysis methods for drug metabolites isolated from biological samples. The DMS-QqQ-MS platform was utilized for the targeted analysis of cocaine and heroin metabolites as well as several other common drug metabolites. The developed methods isolated ions of interest in less than thirty seconds by compensation voltage stepping while Q3 was set to monitor for the presence of the generated fragment ions of interest by SRM. In addition to the methods developed in Chapter 3 for the separation and characterization of drugs of abuse, the rapid profiling of toxicology samples addresses a need for the development of high throughput methods within the area of analytical toxicology.
In an effort to evaluate the effects of ion filtration followed by extended ion trap fill times Chapter 5 presents data which investigate the DMS-Ion Trap platform for the isolation of ionized species followed by selective loading of the ion trap with targeted species from mixtures. To quantify the improvement in dynamic range resulting from DMS filtration, experiments were conducted by varying the trap fill time for samples of increasing complexity from mixed solutions of drugs of abuse to metabolites spiked into biological matrices. A linear dependence of ion accumulation as a function of fill time was observed and, most notably, progressive tenfold increases in trap fill time resulted in corresponding one order of magnitude improvements in precursor ion signal intensity for fill times from 50 ms to 5000 ms. The combination of ion filtration, in tandem with extended trap fill times, increased signal intensities for both precursor (DMS-MS) and product (DMS-MS/MS) ion spectra. The discriminating power of DMS was demonstrated by an observed 100-fold improvement in sensitivity while maintaining quantitative linearity. The data established the value of selective ion filtration by DMS for increasing the capacity of an ion trap and concurrently improved its capabilities for quantitative analysis by MS/MS.
Chapter 6 provides a summary of conclusions from each of the experimental chapters. In addition to presenting the overall conclusions, future directions and experimental approaches are discussed in three distinct areas: forensic science, pharmaceutical science and biomarker analysis. The chapter ends with an epilogue summarizing the dissertation and provides some overall thoughts related to interfacing DMS to MS and the significance of such systems to the analytical community.
Adam Brad Hall
Hall, Adam Brad, "High throughput differential mobility spectrometry – mass spectrometry: fundamental considerations and application development for forensic science" (2012). Chemistry Dissertations. Paper 44. http://hdl.handle.net/2047/d20002672
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