Study On Fabrication Method And Design Of Femtoliter Microreactor Microfluidic Chip

Microreactor was initially defined as a small tubular reactor for water treatment,advanced pharmaceutical,energy,and other industrial research.With the intersection and integration of micro and nano processing and manufacturing technology with chemical and biological domains,nowadays,the concept of"microreactor"generally describes a new category of highly integrated miniaturized chemical and biological reactors.Microfluidic chips fabricated from femtoliter(10^-15L to 10^-18L)level microreactor arrays are used in protein marker detection,gene sequence reading,and nucleic acid detection,etc.The biological reactions performed in the chips are unitarily divided so that the reactions are simultaneously performed in each microreactor and the internal environment of the chip is maintained in the same liquid environment at all times,significantly improving the performance of the microanalytical system and significantly improving the efficiency of reaction analysis and the accuracy of results.In the biological reactions performed on microfluidic microarrays,the reading of long base sequences,for instance,requires repeated exchanges of the liquid environment inside the chip,which is used to advance the reaction and change the reactant class.Under such conditions,the stability of the microparticles carrying the reaction chain to remain in the microreactors directly affects the detection results.Therefore,it is necessary to numerically simulate the structure of the microreactor and design structural parameters that make the reactor more stable for the internal microparticles.Based on the structural model obtained from the numerical simulation,a process study related to the preparation of microreactor arrays using a two-step etching method combining anisotropic etching by dry etching with isotropic etching on a silicon material substrate is carried out to establish a theoretical model to precisely control the structural morphology of the etching,which can provide better stability of the microparticles inside the microreactor under repeated multiple liquid exchanges.The main content of this dissertation is as follows:1.A detailed review of the principle and application scope of the microfluidic chip of the femtoliter microreactor,a description of the research background and significance,and summary of the relevant research status at domestic and abroad,a comparison of different microreactor preparation schemes,and the main research content and methods of this dissertation.2.The simulation model was established to analyze the conventional cylindrical microreactor and Omega（Ω）-shaped microreactor,and to compare the change of lift force when the internal microparticles are at different heights inside the reactor under the condition that the width and height both are identical.3.A fabrication method is a proposal based on inductively coupled plasma（ICP）etching device.Conventional cylindrical microreactors can be fabricated using the standard Bosch etching method,but there is a lack of methodology and related research for the Omega-shaped microreactors.Therefore,it is essential to research the manufacturing process of microreactor array structure,establish the theoretical model of the technological fabrication process,study the influence of process parameters on the microreactor structure,and precisely control its dimensions.In this dissertation,a two-step etching method combining the conventional Bosch etching method of anisotropic etching and isotropic etching was used to successfully prepare Omega-shaped microreactor structures with high homogeneity of silicon-based microreactor arrays.4.The microreactor microfluidic chip is encapsulated by using adhesive bonding.When the adhesive bonding layer has a large number of bubbles,the bubbles could enter the fluid in the flow channel during the biological reaction,which seriously interferes with the acquisition of the biological reaction and detection of optical signals.The factors that affect the number of bubbles in the adhesive layer during the chip encapsulation process are discussed,including the settings of bonding temperature,bonding time,and bonding vacuum,and a more stable and reliable hermetic packaging method is selected for the chip.5.Combined with experimental validation,compared with the chips fabricated by cylindrical microreactors and Omega-shaped microreactors,we tested the performance of microreactors with different morphological contours to enhance the stability of internal microparticles,and successfully detected the first base type after gene fragment matching by the application of Omega-shaped microreactor microfluidic chips to the detection of single bases.