Microfluidic Chip For Synthesis Of CdSe Quantum Dot Encoded Hydrogel Microparticles

With the rapid development of the life sciences, people are paying more attention to the numerous biomedical-related molecules. It is significant to develop a fast and easy method to detect multiple molecules simultaneously. The encoded microparticles can serve as important carriers for analyzing numerous biomolecules. Because of the limitation of decoding techniques, it is difficult to eliminate the interference of the fluorescence signals resulting from the spectra overlap of multicolor in optical encoding methods. As a consequence, it is far from easy to encode through the combination of multi-color with multi-intensity. Therefore, the code number is difficult to increase significantly. Microfluidic synthesis technology provides an important platform for preparing encoded microparticles with various morphologies, which needs less reagent consumption and is easy to operate. In this paper, the flow lithography technology was applied for the synthesis of the CdSe quantum dot (QD) encoded microparticles, and a new encoding strategy combining optical encoding with graphical encoding was developed.In chapter one, advances of the encoding technology and the preparation methods of encoded microparticles were mainly overviewed. The advantages and limitations of current encoding techniques and conventional synthesis methods of encoded microparticles were summarized in detail. The potential advantages of the microfluidic system in preparing encoded microparticles were introduced. The purpose and design of this paper were proposed in the end.In chapter two, multiphase laminar flow technique and flow lithography technique were applied to produce the CdSe QD encoded hydrogel microparticles. A simple shutter device was designed to achieve intermittent exposure. The performance of the system was optimized, and the effects of flow rate and exposure time on the size and morphology of microparticles were investigated. Microparticles with small and uniform size were produced with the flow rate in a range of 0.1-0.3 μL/min and the exposure time in a range of 10-75 ms. With shorter exposure time slower flow rate, smaller and more uniform size were obtained. The length (size along flow direction) of microparticles was 225 μm and the relative standard deviation of microparticle size was 3.7%(n=75) with the flow rate of 0.1 μL/min and expourse time of 75 ms. Furthermore, the effects of modified groups at surface of QDs on the identification of encoded signal were investigated. When the QDs were modified with polyethylene glycol groups, the fluorescence signal of encoded microparticles was more obvious. A variety of CdSe QD encoded microparticles were prepared, and their encoded fluorescent signals were identified. Based on CdSe QD encoded microparticles, a novel encoding method using color, intensity and spatial position was proposed. Finally, the formula for calculating encoding number was expressed according to theoretical inference and experimental verification.In chapter three, the microfluidic method for systhesis of CdSe QD encoded hydrogel microparticles was summarized, and the promising applications of the novel encoding method in bio-analysis and biomedicine were predicted as well.