The three-dimensional quadrupole ion trap (QIT) is an extraordinary device. It functions both as an ion store in which gaseous ions can be confined for a period of time and as a mass spectrometer of considerable mass range and variable mass resolution. Over the past few decades, it has evolved into a powerful tool for both research and routine analysis. The basic objective of this thesis is the development of a three-dimensional quadrupole ion trap with cylindrical symmetry in laminar approximation. The laminar construction allows hyperbolic geometry to be well approximated with minimal construction effort and also provides more access into the trap through interlaminar spaces without disruption of the field. The performance of the trap is examined in the mass selective trapping mode and mass-selective instability mode. Fourier detection is also done. Resolution of our instrument is limited by the external hardware. There is not good enough data quality and so not a good enough spectrum to predict its resolution accurately. A few changes to the instrumentation of the trap will improve the resolution.

No description available.

GnRH peptides have been discovered in a wide variety of vertebrate and invertebrate organisms, and work is ongoing to characterize additional unique isoforms. This dissertation describes the investigation of reversed-phase chromatographic and mass spectrometric behavior of GnRH peptides, the development and application of an LC-MS/MS method for qualitative identification of GnRH peptides, and the comprehensive validation of an LC-MS/MS method for simultaneous, quantitative measurement of hydroxyproline9GnRH (Hyp9GnRH) and mammalian GnRH (mGnRH) in rat brain tissues. Chromatographic and mass spectrometric behavior of GnRH isoforms was characterized for six GnRH model peptides. Using reversed-phase high performance liquid chromatography (HPLC), nearly complete separation of the model GnRH peptides was achieved. Evaluation of electrospray source conditions indicated that certain parameters can be adjusted to affect the abundance of selected charge states and improve response. Using the conditions found to be optimal for GnRH peptides in general, a method was developed to facilitate characterization of novel GnRH isoforms or confirm the identity of known isoforms. Fragmentation patterns for six model GnRH isoforms were examined to determine what portion of the primary sequence could be elucidated by de novo sequencing, and a simple solid phase extraction protocol was developed to isolate the model GnRH compounds from tissue samples. Application of the method to rat brain samples resulted in successful isolation and structural confirmation of hydroxyproline9GnRH and mammalian GnRH. A quantitative method for the determination of concentrations of hydroxyproline9GnRH and mammalian GnRH in rat brain tissue was developed and rigorously validated. Guinea pig brains were found to be a suitable substitute matrix for rat brains, and accuracy and precision were determined after four validation runs. Stability of both peptides in samples over long-term storage and under experimental conditions were evaluated, and the LC-MS/MS method was compared to an enzyme-linked immunoassay. Thirty-one brains from Sprague-Dawley rats were analyzed using the LC-MS/MS procedure and compared to published results for Hyp9GnRH and mGnRH.

Quadrupole ion trap(QIT) mass spectrometry has become one of the most widelyused tools in the analysis of the structure of small molecules. The motion of the ionsstored in the quadrupole ion trap is extremely important. This ion motion within thequadrupole ion trap is controlled by several factors including the m/z ratio and thecollisional cross section of the ion. Investigation of ion motion within the QIT has thepotential to elucidate a new way to separate ions based on these factors. DC tomographyexperiments allow for the trajectory of the ion motion to be measured withoutmodifications to the ion trap. The ability to use DC tomography for separation ofisomeric ions on a commercial GC/MS system was investigated.Investigation of the mass range within the ion trap is necessary for the analysis ofa wide range of molecules. The ability of the quadrupole ion trap to perform MS/MSanalyses can provide insight into the structural information of many compounds.However, there exists a low mass cut-off (LMC) within the quadrupole ion trap and thusinformation about the low m/z fragments from a parent ion is lost. Schwartz and coworkerspresented a new technique labeled pulsed q dissociation (PQD) at the 53rdAnnual ASMS Conference in San Antonio TX in 2005. PQD eliminates the LMC byperforming CID at a qz of 0.4 but, then immediately lowering the q level before the massscan in a linear ion trap. By operating the quadrupole ion trap in this same manner, lowm/z product ions can be detected. This technique and elucidation of the energetic processcontained within PQD were explored further using a modified commercial quadrupoleion trap and the results discussed in this work.

A new approach of making ion trap mass analyzers was developed in which trapping fields are created in the space between two ceramic plates. Based on microfabrication technology, a series of independently-adjustable electrode rings is lithographically patterned on the facing surfaces of each ceramic plate. The trapping field can be modified or fine-tuned simply by changing the RF amplitude applied to each electrode ring. By adjusting the potential function applied to the plates, arbitrary trapping fields can be created using the same set of ceramic plates. Unlike conventional ion traps, the electrodes of planar ion traps have a non-equipotential surface, thus the electric field is independent of electrode geometry and can be optimized electronically. The simple geometry and open structure of planar ion traps address obstacles to miniaturization, such as fabrication tolerances, surface smoothness, electrode alignment, limited access for ionization or ion injection, and small trapping volume, thereby offering a great opportunity for a portable mass spectrometer device. Planar ion traps including the planar quadrupole ion trap and the coaxial ion trap have been designed and tested using this novel method. The planar quadrupole trap has demonstrated a mass range up to 180 Da (Th), with mass resolution typically between 400-700. We have also developed a novel ion trap in which both toroidal and quadrupolar trapping regions are created simultaneously between a set of plates. This "Coaxial Trap" allows trapping and mass analysis of ions in two different regions: ions can be trapped and mass analyzed in either the toroidal or quadrupolar regions, and transferred between these regions. Some simulation work based on the ion motion between two different trapping regions in the coaxial ion trap has been performed. Using a one-dimensional simulation method, ion motion was investigated to transfer ions between these two regions. The effect of the mutipole components in the radial field and axial field, amplitude and frequency of the primary RF and supplementary AC signal were studied to obtain high mass resolution in the axial direction and high transfer efficiency in the radial direction. In all these devices, the independent control of each patterned electrode element allows independent control of higher-order multipole fields. Fields can be optimized and changed electronically instead of physically as is done in conventional traps.

No description available.

This thesis is a numerical study of fields within ion traps having segmented electrodes1. The focus is on two cylindrical ion trap structures, two Orbit rap structures and one planar structure which mimics the field of the Orbit rap. In all these geometries, the segments which comprise the electrodes are easily Machin able rings and plates. By applying suitable potential to the different segments, the fields within these geometries are made to mimic the fields in the respective ideal structures. This thesis is divided into 6 chapters. Chapter 1 presents introduction and background information relevant to this work. A brief description of the Quadrupole Ion Trap (QIT) and the Orbit rap is given. The role of numerical simulations in the design of an ion trap geometry is briefly outlined. The motivation of this thesis is presented. The chapter ends by describing the scope of the thesis. Chapter 2 presents a general description of computational methods used throughout this work. The Boundary Element Methods (BEM) is first described. Both 2D and 3D BEM are used in this work. The software for 3D BEM is newly developed and hence 3D BEM is described in more detail. A verification of 3D BEM is presented with a few examples. The Runge-Kutta method used to compute the trajectory of ion is presented. A brief overview of the Nelder-Mead method of function minimization is given. The computational techniques specifically used to obtain the results in Chapter 3, 4 and 5 are presented in the respective chapters. Chapter 3 presents segmented electrode geometries of the Cylindrical Ion Trap (CIT). In these geometries, the electrodes of the CIT are split into number of mini-electrodes and different voltages are applied to these segmented electrodes to achieve the desired field. Two geometries of the segmented electrode CIT will be investigated. In the first, we retain the flat end cap electrodes of the CIT but split the ring electrode into five mini-rings. In the second configuration, we split the ring electrode of the CIT into three mini-rings and 1The term ‘segmented electrode’ used in this thesis has the same connotation as the term ‘split-electrode’ used in Sonalikar and Mohanty (2013). also divide the end caps into two mini-discs. By applying different potentials to the mini-rings and mini-discs of these geometries we will show that the field within the trap can be optimized to desired values. Two different types of fields will be targeted. In the first, potentials are adjusted to obtain a linear electric field and, in the second, a controlled higher order even multipole field are obtained by adjusting the potential. It will be shown that the different potentials to the segmented electrodes can be derived from a single RF generator by connecting appropriate capacitor terminations to segmented electrodes. The field within the trap can be modified by changing the value of the external capacitors. Chapter 4 presents segmented electrode geometries which are possible alternatives for the Orbitrap. Two segmented-electrode structures, ORB1 and ORB2, to mimic the electric field of the Orbitrap, will be investigated. In the ORB1, the inner spindle-like electrode and the outer barrel-like electrode of the Orbitrap are replaced by rings and discs of fixed radii, respectively. In this structure two segmented end cap electrodes are added. In this geometry, different potentials are applied to the different electrodes keeping top-bottom symmetry intact. In the second geometry, ORB2, the inner and outer electrodes of the Orbitrap are replaced by an approximate step structure which follows the profile of the Orbitrap electrodes. For the purpose of comparing the performance of ORB1 and ORB2 with that of the Orbitrap, the following studies will be undertaken: (1) variation of electric potential, (2) computation of ion trajectories, (3) measurement of image currents. These studies will be carried out using both 2D and 3D Boundary Element Method (BEM), the 3D BEM is developed specifically for this study. It will be seen in these investigations that ORB1 and ORB2 have performance similar to that of the Orbitrap, with the performance of the ORB1 being seen to be marginally superior to that of the ORB2. It will be shown that with proper optimization, geometries containing far fewer electrodes can be used as mass analysers. A novel technique of optimization of the electric field is proposed with the objective of minimizing the dependence of axial frequency of ion motion on the initial position of an ion. The results on the optimization of 9 and 15 segmented-electrode trap having the same design as ORB1 show that it can provide accurate mass analysis. Chapter 5 presents a segmented electrode planar geometry named as PORB used to mimic the electric field of the Orbit rap. This geometry has two planes, each plane consisting of 30 concentric ring electrodes. Although the geometry of PORB does not have conventional inner and outer electrodes of the Orbit rap, it will be shown that by selecting appropriate geometry parameters and suitable potentials for the ring electrodes, this geometry can trap the ions into an orbital motion similar to that in the Orbit rap. The performance of the planar geometry is studied by comparing the variation of potential, ion trajectories and image current in this geometry with that in the Orbit rap. The optimization of applied potentials is performed to correct the errors in the electric field so that the variation of axial frequency of ions with their initial position is minimized. Chapter 6 presents the summary and a few concluding remarks

<div>Amongst the various classes of mass analyzers, the quadrupole ion trap (QIT) is by far the most versatile. Although it can achieve only modest resolution (unit) and mass accuracy (101-102 ppm), it has high sensitivity and selectivity, can operate at pressures exceeding 10-3 torr, is tolerant to various electrode imperfections, and has single analyzer tandem mass spectrometry (MS/MS) capabilities in the form of product ion scans. These characteristics make the QIT ideal for mass spectrometer miniaturization, as most of the fundamental performance metrics of the QIT do not depend on device size. As such, the current drive in miniature systems is to adopt miniature ion traps in various forms – 3D, linear, toroidal, rectilinear, cylindrical, arrays, etc.</div><div><br></div><div>Despite being one of the two common mass analyzers with inherent MS/MS capabilities (the other being the Fourier transform ion cyclotron resonance mass spectrometer), it is commonly accepted that the QIT cannot perform one-dimensional precursor ion scans and neutral loss scans - the other two main MS/MS scan modes - or two-dimensional MS/MS scans. The former two are usually conducted in triple quadrupole instruments in which a first and third quadrupole are used to mass select precursor and product ions while fragmentation occurs in an intermediate collision cell. The third scan can be accomplished by acquiring a product ion scan of every precursor ion, thus revealing the entire 2D MS/MS data domain (precursor ion m/z vs. product ion m/z). This, however, is not one scan but a set of scans. Because the ion trap is a tandem-in-time instrument rather than a tandem-in-space analyzer, precursor ion scans, neutral loss scans, and 2D MS/MS are, at best, difficult.</div><div><br></div><div>Yet miniature mass spectrometers utilizing quadrupole ion traps for mass analysis would perhaps benefit the most from precursor scans, neutral loss scans, and 2D MS/MS because they generally have acquisition rates (# scans/s) an order of magnitude lower than their benchtop counterparts. This is because they usually use a discontinuous atmospheric pressure interface (DAPI) to reduce the gas load on the backing pumps, resulting in a ~1 scan/s acquisition rate and making the commonly-used data-dependent acquisition method (i.e. obtaining a product ion scan for every abundant precursor ion) inefficient in terms of sample consumption, time, and instrument power. Precursor and neutral loss scans targeting specific molecular functionality of interest - as well as 2D MS/MS – are more efficient ways of moving through the MS/MS data domain and thus pair quite readily with miniature ion traps.</div><div><br></div><div>Herein we demonstrate that precursor ion scans, neutral loss scans, and 2D MS/MS are all possible in a linear quadrupole ion trap operated in the orthogonal double resonance mode on both benchtop and portable mass spectrometers. Through application of multiple resonance frequencies matching the secular frequencies of precursor and/or product ions of interest, we show that precursor ions can be fragmented mass-selectively and product ions ejected simultaneously, preserving their relationship, precursor ion -> product ion + neutral, in the time domain and hence allowing the correlation between precursor and product ions without prior isolation. By fixing or scanning the resonance frequencies corresponding to the targeted precursor and product ions, a precursor ion scan or neutral loss scan can be conducted in a single mass analyzer. We further show that 2D MS/MS - acquisition of all precursor ion m/z values and a product ion mass spectrum for every precursor ion, all in a single scan - is possible using similar methodology. These scan modes are particularly valuable for origin-of-life and forensic applications for which the value of miniature mass spectrometers is readily evident.</div>

<p>Conventional mass spectrometry sensing has isomorphic nature, which means measure the input mass spectrum abundance function by a resemble of delta function to avoid ambiguity. However, the delta function nature of traditional mass spectrometry sensing approach imposes trade-offs between mass resolution and throughput/mass analysis time. This dissertation proposes a new field of mass spectrometry sensing which combines both computational signal processing and hardware modification to break the above trade-offs. We introduce the concept of generalized sensing matrix/discretized forward model in mass spectrometry filed. The presence of forward model can bridge the cap between sensing system hardware design and computational sensing algorithm including compressive sensing, feature/variable selection machine learning algorithms, and stat-of-art inversion algorithms. </p><p>Throughout this dissertation, the main theme is the sensing matrix/forward model design subject to the physical constraints of varies types of mass analyzers. For quadrupole ion trap systems, we develop a new compressive and multiplexed mass analysis approach mutli Resonant Frequency Excitation (mRFE) ejection which can reduce mass analysis time by a factor 3-6 without losing mass spectra specificity for chemical classification. A new information-theoretical adaptive sensing and classification framework has proposed on quadrupole mass filter systems, and it can significantly reduces the number of measurements needed and achieve a high level of classification accuracy. Furthermore, we present a coded aperture sector mass spectrometry which can yield a order-of-magnitude throughput gain without compromising mass resolution compare to conventional single slit sector mass spectrometer.</p> / Dissertation

Selective gas-phase dissociation strategies have been developed for the characterization of cross-linked peptides and proteins in quadrupole ion trap mass spectrometers. An infrared chromogenic cross-linker (IRCX) containing a phosphotriester afforded rapid differentiation of cross-linked peptides from unmodified ones in proteolytic digests of cross-linked proteins by selective infrared multiphoton dissociation (IRMPD). Only the cross-linked peptides containing the chromogenic phosphate underwent IRMPD and unmodified peptides were not affected by IR irradiation. IRMPD of IRCX-cross-linked peptides yielded uncross-linked y-ion sequence tags of the constituent peptides due to secondary dissociation of all primary product ions which contained the chromophore, thus allowing successful de novo sequencing of the cross-linked peptides. Peptides cross-linked via a two-step conjugation strategy through the formation of a bis-arylhydrazone (BAH) bond were selectively dissociated by ultraviolet radiation at 355 nm. The BAH-cross-linked peptides could be distinguished from not only unmodified peptides but also dead-end modified peptides based on the selectivity of ultraviolet photodissociation. In a complementary approach, electron transfer dissociation of BAH-cross-linked peptides resulted in preferential cleavage of the hydrazone bond which produced two modified peptides. These modified peptides were subsequently interrogated by CID which allowed for the original site of cross-linking to be pinpointed. IRMPD was implemented in a dual pressure linear ion trap to demonstrate successful photodissociation of peptides having modest absorptivities. Peptides were observed to efficiently dissociation by IR irradiation exclusively in the low pressure cell whereas no dissociation was observed in the high pressure cell due to extensive collisional cooling. IRMPD provided greater sequence coverage of the peptides than CID and yielded product ion mass spectra which were predominantly composed of singly charged product ions which simplified spectral interpretation. IRMPD was further applied for the sequencing of small-interfering RNA. Complete sequence coverage was obtained and the results were compared to CID. / text