Droplet Generation Mechanism And High Throughput Optimization Design Based On Microfluidic Chip

The number of patients with chronic diseases continues to grow worldwide,seriously endangering human health,and there is an urgent clinical need for improved small molecule microsphere formulations with slow and controlled release,targeting,low side effects and high compliance.Droplet microfluidics,as a cutting-edge technology for precise fluid manipulation at the micro-scale,has the advantages of fast droplet production,good homogeneity,and high controllability of continuous production.However,the multiphase fluid flow characteristics,droplet formation and development laws based on microfluidic chips have not been fully understood,and the structural optimization design of droplet microfluidic chips mainly relies on experience and experimental corrections.In addition,the low yield of micron-level single-channel chips limits their industrial application,and the design of high-throughput chips suffers from complex fluid dynamics,large droplet size distribution range,and cell parallel crosstalk.Therefore,this paper addresses the above issues by using theoretical analysis,numerical simulation combined with experimental validation to carry out structural optimization design of high throughput droplet microfluidic chip.The work in this paper will improve the theory of micro-scale liquid-liquid multiphase fluid dynamics and provide a theoretical basis for the optimal design of high-throughput droplet microfluidic systems,and will also provide certain implications for the expansion of microfluidic devices into the field of innovative drug manufacturing and industrial applications.The specific research results are as follows.(1)The numerical model of droplet generation process in flow-focused microfluidic channel is established based on the level set method,and the distribution and evolution of flow field in droplet generation process are studied to reveal the hydrodynamic mechanism of droplet generation;the influence of flow-focused microfluidic channel geometry and flow conditions on droplet generation characteristics is studied,and the results show that:when w*>1,the droplet size gradually increases and the generation frequency gradually decreases with the increase of w*;When w*<1,the droplet size gradually increases and the generation frequency gradually increases with the increase of w*;with the increase of V*,the droplet size gradually decreases and the generation frequency tends to increase,but the larger the w*is,the larger the flow rate ratio for generating stable droplets is.(2)A numerical model of the droplet generation process in parallel with multi-cell is established based on the phase field method,and the effects of capillary number and flow rate ratio on the droplet generation characteristics are investigated.The results show that the droplet size of the coupled system is smaller and the generation frequency is faster than that of the independent unit system at the same flow rate ratio.Two sub-modes in the drop flow regime are identified:dripping-retraction and dripping-retention,and the transition between the two is determined by the capillary number,with the critical capillary number ranging from0.0013 to 0.019.The"synchronous"and"asynchronous"droplet generation modes of the two-cell coupled system are identified,and both the critical capillary number and the critical flow rate ratio V_c*increase with the increase of the dispersed phase flow rate.The dependence of the hysteresis time on the number of droplets is revealed:the larger the capillary number,the shorter the hysteresis time.(3)The kriging agent model optimization design method is used to optimize the microfluidic channel geometry and flow conditions with droplet yield as the optimization objective.The optimized droplet throughput reaches 10153376.61μm~2 s,an increase of19.5%compared to the initial sample value.The droplet throughput is effectively improved.The three-dimensional configuration of the high-throughput droplet microfluidic chip is designed based on the optimal cell structure,including:substrate,dispersed-phase fluid distribution layer,droplet generation layer,continuous-phase fluid distribution layer,and cover sheet.The design of the shared continuous-phase flow channel improves the droplet cell integration and thus the droplet productivity.The strategy of distributing fluid along the center of the chip to both sides reduces along-travel drag losses,reduces the problem of uneven flow distribution,and improves droplet monodispersity.