Study On Design, Fabrication And Application Of Micro Dispensing Array System For Microarray Production

Microarray Analysis is a rapidly developing field in recent years. It is a multidisciplinary technology and derived from Micro Electro Mechanical System (MEMS), biochemistry, analytical chemistry and computing science. The micro dispensing array (MDA) technology is a very important and emerging project in moderate or low density microarray analysis. The arrayed nozzles are fabricated on the silicon wafer or some polymers by employing MEMS technology. The bio-sample spots on slides or membranes can be in process of biochemical reactions after directly dispensed from nozzles. Then, the reactive results are detected and analyzed. The MDA technology that involved the total processes of microarray production, reaction, detection, and analysis, is expectantly applied for life science, drug discovery and clinic medicine in the future.In this dissertation, bio-MDA system has been systematically studied, including feasibility design, microfabrication and improvement, tests of microarray production, and application in microarray assay. The topics of this dissertation are presented below:1. A new project based on the most recent developments of microarray analysis, microarray fabrication, and MDA systems, was proposed.2. The portable accessorial device for the dispensing system was designed and improved, and its ability of sealing was excellent.3. The MDA chips based on several materials and many microstructures were designed and manufactured, and a novel micro dispensing array chip based on three layers and annular interspaces was successfully fabricated. The chip could reduce the reflow phenomenon in channels, and could help droplet formation on the hydrophilic surface. Moreover, the possible contamination within the dispensing units was eliminated.4. The pneumatic pressure control system based on both PC control and four valves were designed and fabricated.5. The test of two MDA systems by two different actuated methods was accomplished. Multilayer SU-8 based micro dispensing chip could simultaneously produce up to 25 individual fluid spots with the average diameters of 384 μm, and the coefficient of variation of spots' diameters was 2.6%. The results demonstrated that the system could produce moderate or low density microarray with good reproducibility, fine uniformity, excellent reliability and high stability.6. The bio-application of our MDA system was studied. The DNA microarrays produced by the system were applid for spot mutative detection, and the protein microarrays were successfully fabricated by the MDA system with the help of the novel buffer mixed by DMSO, borate and PBS in the proportion of 9:1:1.It has been shown that the MDA system has some advantages such as portable, high speed, low sample consuming, as well as chip's design flexibility, and it can be applied for moderate or low density genetic detections and immunoassays.