<p>Advancements in 3D printing technology have provided (1) easy access to low-cost, open- source robotics, and (2) a fast fabrication technique for analytical devices among others. Using the robotics of a 3D printer, a mass spectrometry-based reaction screening device was built as a low- cost, modest throughput alternative to expensive, very fast systems. Using the 3D printer for fabrication, ion mobility devices were fabricated. Fundamental studies of the motion of ions in these devices were performed in addition to applications of ion mobility-mass spectrometry using a 3D printed drift tube ion mobility spectrometer.</p><p><br></p><p>With only simple modification, 3D printer kits provide nearly all the necessary parts for a functional reaction screening device. Replacing the hotend assembly with custom parts to hold a syringe, precise volumes of reaction mixtures can be dispensed, and high voltage applied to the needle for direct analysis of solutions by mass spectrometry. Direct analysis of reaction mixtures in a 96-well microtiter plates was completed in approximately 105 minutes (~65 seconds per reaction mixture, including washing of syringe). Following analysis, product distributions derived from the electrospray mass spectra were represented as heatmaps and optimum reaction conditions were determined. Using low-cost, open-source hardware, a modest throughput for reaction screening could be achieved using electrospray ionization mass spectrometry.</p><p><br></p><p>The manipulation of ions at reduced pressures is very well understood, whereas the efficient manipulation of ions at atmospheric pressure is far less understood. Using 3D printing, multiple iterations of atmospheric pressure drift tube ion mobility spectrometers were fabricated with one and two turns in the drift path. Optimum electrode geometries for ion transmission and resolution were determined by both simulation and experiment. Racetrack effects, where ions on the inside of turns have a shorter path than ions on the outside, were determined to be highly detrimental to resolving power. Drift tubes with two turns in opposite directions (a chicane) corrected for racetrack effects and had only marginally poorer resolving power than a straight drift tube. Additionally, ion intensities were nearly identical between optimized straight and turned ion paths, showing that these manipulations can be done with high efficiency. The focusing of ions at reduced pressure using RF ion funnels at reduced pressure can have nearly 100 percent transmission. At atmospheric pressure, RF fields are not nearly as efficient at focusing ions. By using non-uniform DC fields at atmospheric pressure, ions can be focused, but not nearly to the extent as at reduced pressure.</p><p><br></p><div><div><div><p>The coupling of atmospheric pressure drift tube ion mobility with ion trap mass spectrometry is inefficient due to the mismatch in duty cycle between the two instruments. For this reason, increasing the amount of data collected from a single experiment is of high importance. Fourier transform ion mobility increases the duty cycle from less than 1% to 25%. When ions are fragmented in the mass spectrometer, they maintain the frequency characteristic of the precursor. Therefore, ions can be fragmented without isolation in the ion trap (reducing duty cycle further) and related precursors and product ions identified through their drift time. Two-dimensional tandem mass spectrometry is a method to collect all tandem mass spectrometry information in a single scan. When coupled with ion mobility, this data can be used to generate functional group- specific ion mobility spectra where ion intensity is measured along a precursor or neutral loss scan line. This was demonstrated for a lipid sample in which head-group specific ion mobility spectra were obtained using head-group specific precursor and neutral loss scan lines.</p></div></div></div>

Electrospray ionization (ESI) has become one of the most commonly used ionization techniques for mass spectrometry (MS) and ion mobility spectrometry (IMS), and efforts continue to improve its performance. ESI-MS is most recognized for its wide application to biomacromolecules where high sensitivity is of paramount importance. However, the major limitation in sensitivity with ESI-MS is due to its low ion transmission efficiency from the ESI source into the sampling orifice and through any stages utilized for transfer of ions from atmosphere to vacuum in the MS. A series of atmospheric pressure ion focusing interfaces were designed and implemented to enhance the performance of ESI-MS. The technical objective of this work was to improve sensitivity and detection limits of ESI-MS using a combination of concentric high velocity converging gas flow (aerodynamic focusing) and regulated external electric field (electrostatic focusing) to assist in focusing and transporting ions from the ESI sprayer tip into the sampling nozzle of the MS. The separation time in IMS, based on differing gas phase ion mobilities, ranges from several hundred microseconds to milliseconds. This allows faster analysis than most other conventional separation techniques, such as gas chromatography (GC), liquid chromatography (LC), and capillary electrophoresis (CE). However, the major limitation in ESI-IMS is its low resolution. It is believed that one of the most important contributions to low resolution in ESI-IMS is unwanted ion penetration through the ion gate. In order to solve this ion penetration problem, two mechanical ion gates were designed and optimized to assist in gating sprayed ions from the ESI source into the drift region of the IMS with improved sensitivity and resolution at atmospheric pressure. Applying a voltage to the ion gate and using a high flow drift gas helped to further improve the performance of ESI-IMS. Reduced pressure IMS should help to eliminate clustering and multiple peaks and, hence, improve experimental resolution when using ESI. Therefore, I report the design, construction and evaluation of new IMS systems for reduced pressures. However, the performance of the reduced pressure IMS was not as good as when using atmospheric pressure IMS.