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Mass spectrometry (MS) is a powerful analytical tool that plays crucial roles in many fields, including disease diagnosis, environmental monitoring, drug discovery, and chemical reaction screening and their mechanistic studies. The plethora of applications using MS continue to expand; this, in turn, has enabled continuous explorations that have resulted in the development of innovative ion sources and analyzers. Ambient ionization is a recent innovation that enables direct in-situ complex mixture analysis without having lengthy pretreatment of the sample (e.g., extraction, precipitation, lyophilization). Therefore, direct analysis using ambient ionization reduces analysis time and allows high throughput chemical detection. With such developments in ionization techniques, chemical instrumentation is getting advanced into new applications which were not previously possible. A future outlook on instrumentation is manufacturing portable mass spectrometers. In addition to basic figures of merits of the mass spectrometer, portable mass spectrometer broadens the scope of modern MS due to less power consumption, relatively low cost, and fieldable application. This dissertation describes the development of MS-based applications for clinical diagnosis utilizing ambient ionization and portable mass spectrometer (Chapters 2-4) and reaction screening (Chapter 5). Chapters 2-4 describe the innovations of coupling microfluidic paper-based analytical device (µPAD) to the portable mass spectrometer for ultrasensitive malaria diagnostic. Diagnosis of malaria, which is one of the deadliest infectious diseases, is the primary focus of this dissertation. This disease is encountered in developing countries and other resource-limited settings. Thus, the objective is positioned toward developing an ultrasensitive point-of-care tool so that all people can have equal opportunity to get diagnosed early and accurately. In chapter 2, the use of a portable mass spectrometer became the focus of the work and demonstrated the capability of field study using a mass spectrometer. Less required power consumption, economic burden, and lighter weight of portable mass spectrometer opened another opportunity for chemical detection in low resource settings. In chapter 3, dendrimer-mediated signal amplification technology was developed and applied to the 2D µPAD-MS platform to target asymptomatic diagnosis. The most challenging aspect of eradicating malaria is controlling asymptomatic infection due to no specific symptom and low parasite density. Without control, these asymptomatic infections prompt to generate parasite transmission continuously. Dendrimer contains multiple sites that can link numerous copies of mass tag, enhancing ion signal for MS detection. In chapter 4, next-generation three-dimensional (3D) µPAD was designed and fabricated. Compared to 2D biofluid sampling, a self-sustained and automated 3D µPAD system can serve as a single platform for microsampling, splitting a sample into multiple testing zones, room temperature storage of collected samples and direct MS analysis by paper spray ionization. Lastly, chapter 5 develops a novel nano-atmospheric pressure chemical ionization (APCI) source for monitoring and screening gas-phase chemical reactions. The ionic wind from corona discharge in APCI provides relatively high-energy electrons, which enable numerous collisions at atmospheric pressure. Abundant collisions led to an efficient uncatalyzed N-alkylation reaction for various primary amine compounds (e.g., propyl-, butyl-, hexyl-, and cyclohexylamine). By performing the reactions at atmospheric pressure, not only were we able to monitor reactions in real-time using mass spectrometry, but the following gas-phase reaction products were collected and offered for preparative-scale opportunities.

Rapid Diagnostic tests (RDTs) products for malaria available on market today are all blood-based. Massive research have been done to find a cheap and convenient method to diagnose malaria using saliva samples. In this project, an innovative approach by converting electrochemical impedance change to voltage difference variation was demonstrated. Through the functionalization of Au electrode surface with pLDH aptamers and construction of Wheatstone bridge using interdigitated electrodes, a significant voltage difference was measured which showed potential for not only qualitative but also for quantitative detection of malaria utilizing saliva specimen. An electrical circuit prototype was also assembled demonstrating the feasibility of making a portable device for measurement.

Abstract: Data based abnormality detection is a growing research field focussed on extracting information from feature rich data. They are considered to be non-intrusive and non-destructive in nature which gives them a clear advantage over conventional methods. In this study, we explore different streams of data based anomalies detection. We propose extension and revisions to existing valve stiction detection algorithm supported with industrial case study. We also explored the area of image analysis and proposed a complete solution for Malaria diagnosis. The proposed method is tested over images provided by pathology laboratory at Alberta Health Service. We also address the robustness and practicality of the solution proposed.