Development of Capillary Vibrating Sharp-Edge Spray Ionization for Improving Continuous Flow Mass Spectrometry Analysis

Capillary Vibrating Sharp-Edge Spray Ionization (cVSSI) is new ionization technique developed in the year of 2018. This ionization technique has attractive features such as simplicity, compactness, ease of manipulation, low costs, compatible with continuous flow, etc. However, the development of high performance cVSSI for mass spectrometry analysis is a process that needs unremitting optimizations. In this dissertation, I demonstrate the development of cVSSI for improving continuous flow mass spectrometry analysis. The chapter 2 focuses on improving the ionization efficiency of cVSSI through reducing the droplet size. Three strategies were tested to reduce the droplet size of VSSI. The most effective strategy was by replacing the 100 μm internal diameter (I.D) capillary with a small I.D. pulled capillary. With this strategy, the average droplets size was reduced to ~ 5 μm and the sample consumption was reduced by ~ 30-fold. Electrospray ionization (ESI) is often affected by corona discharge when spraying 100 % aqueous solutions, especially under negative ion mode. In Chapter 3, field enabled cVSSI was introduced to improve the performance of ESI under negative ion mode. Compared with commercial ESI source using nebulization gas to reduce discharge, 10−100-fold enhancement in signal intensity and 3−10-fold improvement in S/N are achieved for various kinds of molecules including DNA, peptides, proteins, and oligosaccharides. The presence of salt ions in sample solution is detrimental for the MS analysis. To achieve the optimal MS detection results, desalting is necessary for samples with high salt concentrations. In chapter 4, a rapid, low cost and flexible on-line desalting method using Nafion coated melamine sponge and with cVSSI as ionization technique was developed. Effective online desalting of a 10 mM NaCl solution was demonstrated for a wide range of molecules including small molecules, peptides, DNAs, and proteins under a flow rate of 10 µL/min. The vibrating sharp edge glass capillary has been applied to MS analysis, CE-MS analysis, mixing and droplets generation. However, the working mechanism of vibrating sharp edge glass capillary is still unknown. In chapter 5, we studied the impact of liquid inside the vibrating glass capillary on its streaming patterns. Results show that the liquid inside the glass capillary can change the streaming patterns as well as the streaming velocity. The COMSOL simulation for streaming patterns matches with the experimental observed streaming patterns for both the liquid-filled tip and air-filled tip. With higher streaming velocity generated by liquid-filled tip, we demonstrate its high performance for mixing and droplets generation. This study will provide useful guidance when optimizing the working efficiency of cVSSI device. Chapter 6 is a future direction for cVSSI. Compared with ESI, the cVSSI can provide improved performance for MS analysis under certain conditions. One question is whether the cVSSI is even a softer ionization technique than ESI. A strategy that using the “thermometer ions” to study the internal energy of ions produced by cVSSI was proposed, and the internal energy of cVSSI will be compared with the internal energy of ESI to valid its softness. The internal energy study of cVSSI will be important for its applications toward labile compound analysis, native MS studies and non-covalent interactions. Overall, the cVSSI is a novel and reliable ionization technique for high performance continuous flow MS analysis