Development And Applications Of “Mass Spectrometry Sensors” Based On Paper Spray Ionization Of Microdroplets

Developing analytical techniques with high selectivity, high sensitivity and rapid temporal response is a prerequisite for chemical monitoring of complex micro-environments. However, commonly used methods, such as electrochemical and optical sensors, usually target known compounds, and activated responses of the analytes are required. Mass spectrometry(MS) is a label-free, molecular-specific, sensitive and universe analytical method, therefore, development of MS as a sensor is apparently of great importance.In this thesis, based on the paper spray ionization of continuous microdroplets, a novel ―MS sensor‖ was developed, as well as an online integrated platform in combination with microfluidics. Utilizing these methods, several bioanalytical applications were performed. The main points are as follows:First, the state of the art and technical bottlenecks in the field of microdroplet-based system, microfluidics and mass spectrometry were summarized and discussed, illustrating the significance of developing ―MS sensors‖.Utilizing gravity and electrostatic attraction as the driving forces, generation and online paper spray ionization-MS analysis of sub-microlitre droplets were introduced. The parameters affecting the volumes and frequency of the microdroplets were investigated. Each microdroplet would produce an individual peak in the ion chromatogram. This proposed ―MS sensor‖ was successfully applied to the monitoring of an amine-aldehyde condensation reaction and direct analysis and distribution of molecules in fruits, which preliminarily indicated its potential.Moreover, with thinner capillary tubes, smaller droplets were generated. A homemade microdialysis module was introduced to establish a microdialysis-paper spray ionization-MS system. Besides, it was found that utilization of silica-coated paper could remarkably improve the performance of paper spray ionization. For microdroplets at 50 n L, a highest resolution at about 1.5 s was achieved. Online monitoring of glucose concentration in cell culture mediums was performed. As a model, hormone regulation of the glucose concentration was investigated.To establish an automatic and online multi-channel microfluidic chip-MS platform, a device was designed and fabricated for microsampling by a capillary. The movement of the capillary was programmed by a computer to aspirate samples from different microfluidic channels, in the form of microdroplets(typically tens of nanolitres in volume), which were separated by air plugs. After demonstrating the feasibility and analytical performance of the method by a concentration gradient experiment, association constant within a noncovalent protein-protein complex was determined.Furthermore, a module for cell culture was integrated to investigate cell metabolism by online microfluidic chip-MS, employing lactate efflux as a model. Three aspects were focused: real-time monitoring of the cellular metabolites, differential effects of a drug on cells of different types, and the dose-response information of a drug. The potential of this platform in cell analysis was exhibited.