Improvements to the analytical performance of ion trap mass spectrometry

Mass spectrometry is a powerful analytical technique that is capable of a wide range of chemical and biological analyses. The quadrupole ion trap mass spectrometer (QITMS) is known for its ruggedness, sensitivity, and high efficiency for tandem mass spectrometry (MS/MS) experiments. Non-idealities in electrode geometry result in small contributions of higher order fields (HOFs) to the primary quadrupolar electric field of the ion trap. These HOFs have been useful in enhancing the resolution, MS/MS efficiency, and sensitivity in the QITMS. A portion of the work presented in this dissertation is intended to serve as a basis for improved ion trap performance through the judicious use of HOFs. Development of rf circuitry and characterization of a compensated cylindrical ion trap (CCIT) mass spectrometer, designed for studying the effects of HOFs, are also described herein. An additional set of grounded electrodes was introduced into the CCIT instrument to remove detrimental effects of capacitive coupling and HOFs were successfully introduced. Mass spectra acquired after the introduction of HOFs showed improvements to the injection efficiency over a broad range of rf voltages. The optimal conditions for resonance ejection in the CCIT occurred at an octapole HOF non-linear resonance, which gave improvements both to mass resolution and sensitivity (i.e., the number of ions detected). Resonance ejection performed at an octapole non-linear resonance was successful in improving the sensitivity of the CCIT for the analysis of volatile organic compounds in the presence of a heavy buffer gas. A novel higher order field ion trap, possessing predominantly octapole fields, was developed. This octapole ion trap exhibited higher trapping capacity than a quadrupole ion trap of similar geometry. However, mass analysis in the octapole ion trap was not achievable because ions were resonantly ejected over a broad frequency range. A second generation octapole ion trap, with improved resonance ejection characteristics, also was developed. Resonance ejection experiments in this geometry were in agreement with ion trajectory simulations, but mass analysis using resonance ejection was again not possible due to broad band ejection. A non-destructive Fourier transform detection method was simulated and found to be viable

Book Reviews

Book Reviews by Charles S. Desmond, Godfrey P. Schmidt, Robert E. Sullivan, Louis C. Kaplan, and Paul C. Bartholomew

Pulsed Nano-Electrospray Ionization: Characterization of Temporal Response and Implementation with a Flared Inlet Capillary

The temporal response of pulsed nano-electrospray ionization mass spectrometry (nano-ESI-MS) was studied and its influence on ion formation and detection was characterized. Rise and decay times for the mass resolved ion current were determined to be 20 ± 3 msec and 61 ± 5 msec, respectively, which led to a maximum pulse rate of 12 Hz. Pulsed nano-ESI operation was demonstrated from a multi-sprayer source controlled by a high voltage pulsing circuit constructed in-house. The desired source mode of operation (e.g. pulsing or continuous) can be realized solely by controlling the voltage applied to each sprayer

Acute hepatic failure and multi-system organ failure secondary to replacement of the liver with metastatic melanoma

BACKGROUND: Metastatic malignant melanoma to the liver resulting in fulminant hepatic failure is a rare occurrence. CASE PRESENTATION: A 46 year old man presented to hospital with massive hepatomegaly, elevated liver enzymes and increased lactate three weeks following resection of a malignant melanoma from his shoulder (Clark level 5). Initially stable, he decompensated 24 to 48 hours subsequent to presentation with respiratory failure requiring mechanical ventilation, distributive shock requiring high dose vasopressor infusion, coagulopathy refractory to plasma infusion, progressive rise in liver enzymes and severe metabolic abnormalities including hyperkalemia, acidosis, hyperphosphatemia, hyperuricemia and hypocalcemia. Refractory to aggressive physiologic support he received palliation. Autopsy revealed >80% liver infiltration by metastatic malignant melanoma. CONCLUSION: We report a case of fulminant hepatic failure secondary to metastatic malignant melanoma infiltration of the liver

The autism inpatient collection: Methods and preliminary sample description

© 2015 Siegel et al. Background: Individuals severely affected by autism spectrum disorder (ASD), including those with intellectual disability, expressive language impairment, and/or self-injurious behavior (SIB), are underrepresented in the ASD literature and extant collections of phenotypic and biological data. An understanding of ASD's etiology and subtypes can only be as complete as the studied samples are representative. Methods: The Autism Inpatient Collection (AIC) is a multi-site study enrolling children and adolescents with ASD aged 4-20 years admitted to six specialized inpatient psychiatry units. Enrollment began March, 2014, and continues at a rate of over 400 children annually. Measures characterizing adaptive and cognitive functioning, communication, externalizing behaviors, emotion regulation, psychiatric co-morbidity, self-injurious behavior, parent stress, and parent self-efficacy are collected. ASD diagnosis is confirmed by the Autism Diagnostic Observation Schedule - 2 (ADOS-2) and extensive inpatient observation. Biological samples from probands and their biological parents are banked and processed for DNA extraction and creation of lymphoblastoid cell lines. Results: Sixty-one percent of eligible subjects were enrolled. The first 147 subjects were an average of 12.6 years old (SD 3.42, range 4-20); 26.5 % female; 74.8 % Caucasian, and 81.6 % non-Hispanic/non-Latino. Mean non-verbal intelligence quotient IQ = 70.9 (SD 29.16, range 30-137) and mean adaptive behavior composite score = 55.6 (SD 12.9, range 27-96). A majority of subjects (52.4 %) were non- or minimally verbal. The average Aberrant Behavior Checklist - Irritability Subscale score was 28.6, well above the typical threshold for clinically concerning externalizing behaviors, and 26.5 % of the sample engaged in SIB. Females had more frequent and severe SIB than males. Conclusions: Preliminary data indicate that the AIC has a rich representation of the portion of the autism spectrum that is understudied and underrepresented in extant data collections. More than half of the sample is non- or minimally verbal, over 40 % have intellectual disability, and over one quarter exhibit SIB. The AIC is a substantial new resource for study of the full autism spectrum, which will augment existing data on higher-functioning cohorts and facilitate the identification of genetic subtypes and novel treatment targets. The AIC investigators welcome collaborations with other investigators, and access to the AIC phenotypic data and biosamples may be requested through the Simons Foundation (www.sfari.org)

From flying rockets to Tesla: examining the sustainable mobility preferences of primary school children in Denmark and the Netherlands

The relationship between children and cars is not directly obvious, but they are a core group of passengers moving daily from and to school and they are future potential buyers. Moreover, many of the values, worldviews, and patterns of energy (and mobility) consumption enshrined in adults become formed and perhaps cemented in childhood. Lastly, children are not directly concerned with many of the choices and information that adults handle, so measuring what they know could proxy for popular knowledge in society. This paper offers a first international comparison between 587 surveyed schoolchildren between 9-13 years of age in Denmark and the Netherlands on EV knowledge and current and future car transport. Results indicate that national and regional context matter, as do gender, age, and to a certain extent the level experience with low-carbon innovations such as electric vehicles. In general, however, children rank the environmental impact of cars just below personal safety and we can conclude that they are aware of EVs and their main benefits. Simultaneously, they also know that EVs are costlier to purchase. Most important, the children overwhelmingly agree on the future direction of car-based transport with cars that are safer, more energy efficient and alternatively fueled

A spatial temporal analysis of the Fusarium graminearum transcriptome during symptomless and symptomatic wheat infection

Fusarium head blight of wheat is one of the most serious and hazardous crop diseases worldwide. Here, a transcriptomic investigation of Fusarium graminearum reveals a new model for symptomless and symptomatic wheat infection. The predicted metabolic state and secretome of F. graminearum were distinct within symptomless and symptomatic wheat tissues. Transcripts for genes involved in the biosynthesis of the mycotoxin, deoxynivalenol, plus other characterized and putative secondary metabolite clusters increased in abundance in symptomless tissue. Transcripts encoding for genes of distinct groups of putative secreted effectors increased within either symptomless or symptomatic tissue. Numerous pathogenicity‐associated gene transcripts and transcripts representing PHI‐base mutations that impacted on virulence increased in symptomless tissue. In contrast, hydrolytic carbohydrate‐active enzyme (CAZyme) and lipase gene transcripts exhibited a different pattern of expression, resulting in elevated transcript abundance during the development of disease symptoms. Genome‐wide comparisons with existing datasets confirmed that, within the wheat floral tissue, at a single time point, different phases of infection co‐exist, which are spatially separated and reminiscent of both early and late infection. This study provides novel insights into the combined spatial temporal coordination of functionally characterized and hypothesized virulence strategies

Plasma Dynamics

Contains reports on four research projects.National Science Foundation (Grant ECS82-13485)University of Maryland (Subcontract A200728)U.S. Air Force - Office of Scientific Research (Grant AFOSR-84-0026B)U.S. Department of Energy (Contract DE-ACO2-78-ET-51013)National Science Foundation (Grant ECS82-13430