Research On COC Matrix Microfluidic Chip For Liposome Nanoparticle Synthesis

In this paper,liposome nanoparticle synthesis technology was combined with microfluidic technology to prepare a microfluidic chip for liposome nanoparticle synthesis research.Liposome nanoparticles were prepared by taking advantage of the characteristics of continuous flow of microfluidic chips and short diffusion distance in microchannels.In this study,Egg PC +cholesterol,2-oleoyl-1-palm-tin glycerol-3-phosphocholine(POPC)were used as the phospholipid layer materials for the synthesis of liposome nanoparticles,ethanol was used as the organic solvent,and the solvent dilution method was used to prepare liposome nanoparticles in the microfluidic chip made of COC.The main research contents are as follows:(1)Structural design and numerical simulation of microfluidic chips for liposome nanoparticle synthesis.Referring to the commonly used fluid mixing chip structure,six microfluidic chips with different mixing structures were designed.COMSOL numerical simulation was used to investigate the effects of different mixing structures and different total flow rates on the mixing efficiency of liposome nanoparticles.Considering the conditions required for injection molding,the model with the best results was selected for mold preparation and injection molding.(2)Study on bonding method of COC matrix injection molding chip.In order to seal the chip with fluid channel formed by injection molding,clamping assisted bonding,adhesive bonding,chemical solvent melting assisted by hot pressing and other bonding methods are tried.The bonding mode with good sealing and less influence on the flow channel was selected for chip bonding.(3)Experimental study on synthesis of liposome nanoparticles based on microfluidic chip.Two lipids,5mg/m L phosphatidylcholine +2.5mg/m L cholesterol and 5mg/m L POPC,were used as the required phospholipids for the synthesis of liposome nanoparticles.The effect of different flow rates on the synthesis of liposome nanoparticles was investigated by injecting phospholipid soluble ethanol phase solution and PBS aqueous phase buffer solution into the microfluidic chip under the flow rate ratio of ethanol phase:PBS aqueous phase = 1:3.The experimental results showed that the particle size of liposomal nanoparticles generated by phosphatidylcholine +cholesterol phospholipids was smaller than that generated by POPC phospholipids at the same flow rate.With the increase of the total flow rate,the particle size of the two liposome nanoparticles showed a decreasing trend.The method used in this study was compared with the syringe ethanol dilution method and stirring ethanol dilution method,and the particle size and particle size distribution of the produced liposome nanoparticles were analyzed.The simulation and experimental results are of great significance for the optimization of microfluidic liposome nanoparticle synthesis technology.