Microfluidic Flow Control Systems For Cell Analysis On Microchips

With the development of science and technology, the traditional method of cell analysis can no longer meet the requirements for modern cell analysis. Thus the development of novel cell analysis approaches has become an important subject in the field of analytical and biological sciences. The appearance of microlfuidics has overcome the restriction of traditional analytical methods, by reducing the analytical systems to micrometer scale and controling the fluid in micro-scale by various techniques, which realized the microscale, controllable, rapid and efficient separation and analysis in the flow mode. It shows great potential in cell analysis. As microfluidic control is the core technology in microfluidics, it is of vital significance to develop new microfluidic control methods in cell analysis for both extending the application of microfluidics and promoting the level of cell analysis. The present work aims at investigating novel microfluidic flow control techniques for microfluidic cell analysis.In Chapter1, the microfluidic flow control techniques for cell analysis were summarized. The microfluidic flow control methods for the cell culture and cell analysis in microfluidic chips were introduced in detail, including the microfluidic driving for the perfused culture of cell, the generation of concentration gradients in microfluidic chips and the generation of concentration gradient droplets in microfluidic chips.In Chapter2, a micropump based on osmotic effect was developed, and the stability of its flowrate, working time and micropump pressure were investigated. The micropump features simple structure, small volume, power-free and pulse-free. By integrating onto the microfluidic chip, the micropump was used to realize the perfused culture of human colorectal carcinoma CCL-187cells and in-site specific immunofluorescence assay. The experimental results demonstrated that the cells grow well on the chip system.In Chapter3, a large-scale integrated concentration gradient chip was presented. The chip has high density of channel network, and is capable of generating hundreds of stable gradient concentrations in20s. It features various gradient modes, quantitative concentrations in branch channels and the small size of chip despite the increase of branch channel number. When used for drug induced cell apoptosis assay, the chip generated64concentrations of single drug for inducing HeLa cell apoptosis in a single operation, and simultaneously generated and tested192concentrations of drugs, including gradients of two individual drugs and one gradient of a two-drug mixture.In Chapter4, a chip for generating concentration gradient droplets was proposed. For a chip with2inlets and5levels,64sets of droplets with33gradient concentrations were generated. The average diameter of droplets was40-50μm, the average volume of droplets was50pL, and the RSD of the droplet sizes in different sets was below7%. When used for the preparation of gold and silver alloy nanoparticles,33alloy nanoparticles with different content ratios of gold and silver were produced. The nanoparticles can be used for cell analysis by serving as the encoding cell labels with multi-concentration and multi-color characteristics.