Mass Spectrometry And Liquid Chromatography Analysis Based On Microfluidic Droplet Systems

In recent years, the research in droplet-based microfluidics has made great progress. Various techniques for generation and manipulation of droplets have been developed. Droplet-based microfluidic systems have become an important platform for microscale chemical and biological researches, and have been successfully applied in protein crystallography, chemical synthesis, cell biology and analytical chemistry. Currently, one of the bottleneck of droplet-based microfluidic systems lies in the lack of high-information-content detection methods for droplets, such as mass spectrometry.In Chapter 1, the current progress and application in chemistry and biology of droplet-based microfluidic systems are reviewed. Various droplet manipulation techniques are comprehensively described including droplet generation, sample and reagent injection, mixing, droplet fission, droplet trapping, droplet storage and droplet sorting. The analytical techniques for droplet detection based on optical, electrical, capillary electrophoresis and mass spectrometry are discussed.In Chapter 2, an integrated interface combining glass chip with electrospray ionization mass spectrometry (ESI-MS) was developed. A low-melting-point alloy molding method was used to achieve the electrical contact in the interface, which overcame the difficulty in the fabrication of microelectrode on glass chip. An improved fabrication approach for monolithic emitter tip based on pyramid-shaped tip configuration and stepped grinding was also developed to fabricate sharp tips with a smallest tip size of ca.15x50μm. The performance of the emitter was evaluated in the analysis of reserpine, angiotensinⅡand myoglobin. The advantages of the present interface include ease of fabrication, low cost, high sensitivity and stability, and long lifetime.In Chapter 3, an ESI-MS-based droplet analysis system was developed using the monolithic emitter described in Chapter 2. A hydrophilic tongue-based droplet extraction interface was developed, which could extract droplets from oil stream to aqueous stream for MS analysis with high reliability and controllability. The analytical performance was evaluated using angiotensin as model sample. The sensitivity was comparable to the previously reported results and a good repeatability of 5.2% RSD (n=7) was obtained. Furthermore, the present device was applied in on-line monitoring the microscale alkylation reaction of peptide in droplets.In Chapter 4, a novel type of miniaturized liquid chromatography system namely droplet-array liquid chromatography was presented. Two picoliter-scale droplet arrays were generated on the both sides of microchannel using droplet trapping technique, which were serving as the stationary phase of liquid chromatography. The design of the droplet trapping microstructures, as well as the effects of flow rate of mobile phase, effective separation length, and sample injection volume, were systematically investigated and optimized. The performance was demonstrated in the separation of two polycyclic aromatic hydrocarbon compounds. The present system has advantages of large sample capacity, simple structure, and low pressure.