With the continued evolution of MEMS-based gas chromatography, the drive to develop new standalone systems with lower power consumptions and higher portability has increased. However, with improvements come tradeoffs, and trying to reduce the pressure drop requirements of previously reported semi-packed columns causes a significant sacrifice in separation efficiency. This thesis covers the techniques for evaluating the separation column in a gas chromatography system as well as the important parameters that have the most effect on a column’s efficiency. Ionic liquids are introduced as a stable and versatile stationary phase for micro separation columns. It then describes a MEMS-based separation column design utilizing density modulation of embedded micro-pillars which attempts to optimize the balance between separation efficiency and pressure drop. / Master of Science / Gas chromatography is a technique used by scientists to separate and identify chemical compounds present in a given test mixture. It is a versatile technique that can be used for qualitative and quantitative analysis of complex mixtures in a variety of applications. However, typical gas chromatography systems are confined to a lab because they are large and consume a lot of power. In order to overcome these problems, different research groups have focused their attention towards the development of portable MEMS-based gas chromatography systems. By miniaturizing the various components of a gas chromatography system, these two main issues can be alleviated. This thesis covers the strategies used to develop and evaluate the separation column of a gas chromatography system and introduce a new MEMS-based column design that will further reduce the power consumption.

Monoclonal antibodies are large, complex biomolecules that can be difficult to characterize. Characterization is important because of the various post translational modifications that can occur during manufacturing, processing, and storage. Some modifications can lead to efficacy and safety issues and therefore are heavily monitored. A leading way to monitor various modifications is by using liquid chromatography. The high sensitivity, reproducibility, and ability to quantitate analytes makes it very attractive for monoclonal antibody characterization. The large molecular size of monoclonal antibodies (150 kDa) makes them challenging to separate efficiently and with high enough resolution to be helpful. New column technologies that would help improve protein separation efficiencies and slectivities would greatly help in this challenging process. In this thesis, three novel bonded phases are developed for the separation of monoclonal antibodies including a weak anion and cation exchanger (WAX, CEX) for the separation of charged species as well as a novel hydrophilic interaction chromatography (HILIC) for the separation of glycoforms. Column develop is achieved by optimizing selectivity and improving efficiency of separations by altering particle surface chemistry.

Instrument miniaturization is led by the desire to perform rapid diagnosis in remote areas with high throughput and low cost. In addition, miniaturized instruments hold the promise of consuming small sample volumes and are thus less prone to cross-contamination. Gas chromatography (GC) is the leading analytical instrument for the analysis of volatile organic compounds (VOCs). Due to its wide-ranging applications, it has received great attention both from industrial sectors and scientific communities. Recently, numerous research efforts have benefited from the advancements in micro-electromechanical system (MEMS) and nanotechnology based solutions to miniaturize the key components of GC instrument (pre-concentrator/injector, separation column, valves, pumps, and the detector). The purpose of this dissertation is to address the critical need of developing a micro GC system for various field- applications. The uniqueness of this work is to emphasize on the importance of integrating the basic components of μGC (including sampling/injection, separation and detection) on a single platform. This integration leads to overall improved performance as well as reducing the manufacturing cost of this technology. In this regard, the implementation of micro helium discharge photoionization detector (μDPID) in silicon-glass architecture served as a major accomplishment enabling its monolithic integration with the micro separation column (μSC). For the first time, the operation of a monolithic integrated module under temperature and flow programming conditions has been demonstrated to achieve rapid chromatographic analysis of a complex sample. Furthermore, an innovative sample injection mechanism has been incorporated in the integrated module to present the idea of a chip-scale μGC system. The possibility of using μGC technology in practical applications such as breath analysis and water monitoring is also demonstrated. Moreover, a nanotechnology based scheme for enhancing the adsorption capacity of the microfabricated pre-concentrator is also described. / Ph. D.

This thesis in microscale gas chromatography (μGC) creates a paradigm shift in rapidly analyzing chemicals in the environment or analytes. We are looking for unexpected chemical changes that have been added purposefully or unintentionally. The work examines various aspects of μGC technology, including the optimization of ionic liquid stationary phase coatings for microfabricated columns, achieving up to 8300 theoretical plates per meter for naphthalene using 1-butylpyridinum bis(trifluoromethylsulfonyl)imide [BPY][NTf2] at 240°C. The development of portable systems for fuel adulteration detection is demonstrated, capable of discriminating 5% kerosene adulterated diesel fuel with four seconds of chromatogram analysis. The research also presents a novel parallel column configuration using three ionic liquid-coated semi-packed columns, each 1 m long and 240 μm deep, for complex gas analysis of up to 46 compounds. Key innovations discussed include optimized coating procedure of GC separation columns and implementation of GC based miniaturized electronic nose with the integration of machine learning algorithms. An evaluation of a prototype modular electric and fluidic μGC was evaluated and validated for benzene toluene, ethylbenzene, and xylene (BTEX). This research highlights the versatility of μGCs in applications ranging from environmental monitoring to quality control in the fuel industry, showcasing their potential as powerful tools for on-site chemical analysis with improved selectivity, resolution, and portability. / Doctor of Philosophy / This thesis advances the development of miniature chemical analytical systems, specifically gas chromatography, which is the gold standard for detecting volatile organic compounds in the environment. The work encompasses comprehensive improvements to these systems, from optimizing fabrication and coating of separation columns for better chemical separation to developing rapid prototyping methods for both hardware and software components. Through the integration of machine learning and innovative system designs, the thesis demonstrates significant improvements in detection capabilities, including identifying fuel tampering within seconds and monitoring harmful air pollutants at parts-per-billion levels over extended periods. These advances pave the way for making sophisticated chemical analysis accessible outside of traditional laboratories, enabling direct testing at locations where immediate results are crucial for safety and quality control.