Research On Key Technologies Of Integrated Dielectrophoresis Detectetion Chip System

Microfluidic chip is one of the most important development directions among theBio-MEMS (Bio-Micro-electromechanical System). Dielectrophoresis Chip (DC),which is based on invasive cell operation and has the advantage of keeping cellphysiological activity, is always the research hotspot and fronts for studying andmanipulating cells and bacteriain in the micro environment.Based on study the background of the DC technology, this dissertation aiming atthe problem of integrating the cell enrich, separation, detection analysis, and chipsystem, proposed a novel plan and new method of developing DC system that integratsdielectrophoresis enrich microelectrodes, microchannel network, on-line detectionsystem together; it was studied the factors that effect the dielectrophoresis enrichprocess, and the continuous separation condition for dielectrophoresis force and fluidforce coupling technique; it was also established the electric model and fluid model forDC based on interdigitated microelectrodes array and hydrodynamic focusing principle,respectively, and the overall design for the DC was determined by solving these models;it was proposed a new idea of integrating on-line dual detection system that LEDinduced transmitted fluorescence detection system and impedance sensor together onthe DC system; based on the MEMS fabrication platform in the lab, by finishing layoutand fabrication process design, and by combining the peripheral control circuit,detection circuit together, it was successfully developed a prototype of integrateddielectrophoresis chip detection system. Using the mixed red blood cells andHepatocarcinoma cells as experiment sample, the main function of the integrateddielectrophoresis chip detection system was verified.The main contributions of this work are listed as follows:①Based on reviewing literature and references on DC and its detectiontechnology, the main problems on the current DC analysis system were pointed out.Motivated by the above observation, the research objectives and contents of this workwere developed, respectively;②It was studied the dielectrophoresis enrich mechanism and the effect factors,and the continuous separation condition for dielectrophoresis force and fluid forcecoupling technique was discussed; it was innovatively proposed a new idea ofintegrating on-line dual detection system which includes LED induced transmitted fluorescence detection system and impedance sensor together on the DC system;③It was established the electric model and fluid model for DC based oninterdigitated microelectrodes array and hydrodynamic focusing principle, respectively,and the overall design for the DC system was determined by solving these models; Itwas set up the LED induced transmitted fluorescence detection system and impedancesensor was designed.④Based on the MEMS fabrication platform in the lab, by finishing fabricationprocess and layout design, the integrated dielectrophoresis detection chip wassuccessfully developed, which was satisfied with the design index. It was accomplishedthe integrated dielectrophoresis detection chip, optical/electric on-line dual detectionsystem, control circuit and other modules integrated together, and successfullydeveloped a prototype of integrated dielectrophoresis detection chip system.⑤The application experiments based on the developed integrateddielectrophoresis detection chip system were studied. Using the Hepatocarcinoma cellsand human trabecular meshwork endothelium cells as experiment sample respectively, itis verified the single cell response ability for LED induced transmitted fluorescencedetection system, and the ability which can monitor cell physiological status by theintegrated impedance sensor. Using the suspension that mixed red blood cells andHepatocarcinoma cells together as experiment sample, the dielectrophoresis in situenrich, continuous separation, online dual detection experiments were done. The resultsshowed that the nDEP in situ enrich efficiency for Hepatocarcinoma cells can reach to87.5%, and the capture efficiency for Hepatocarcinoma cells in the mixed cellsuspension is greater than85%. The compact fluorescence detector and the integratedimpedance detector accomplished the functions of cell number counting detection andcell physiological state online identification, respectively, which demonstrated thefeasibility and validity of the developed integrated dielectrophoresis detection chipsystem.