Development Of Flow-Field Flow Microfluidic Device For Exosomes Separation

Exosomes were firstly discovered in the 1980 s and had been regarded as waste excreting by cells.However,with the further study of exosomes,it had been found that the exosomes had profound significance in the immune response,antigen presentation,cell migration,cell differentiation and tumor invasion.In order to better understand exosomes,it is an indispensable step to separate them from mixed impurities.So a simple,efficient and cost-effective exosomes separation technology is needed.In this study,a set of flow field flow microfluidic separation devices for separating exosomes from other protein components was designed and processed.Starting from the principle of the method,the important parameters in each study are derived.Simulation analysis was conducted by using multi-physics coupled simulation software,which provided a basis and method for subsequent physical device fabrication and separation of sample components.First of all,this study made a systematic explanation of the basic concept of Field Flow Fractionation(FFF),and then introduced the key parameters of Flow Field Flow Fractionation(FlFFF).In the simulation,in order to obtain the factors affecting the FlFFF,the normalization method was used to change the height,length,width of the channel and component particle size to compare the separation effects of the exosomes and Bovine Serum Albumin(BSA).In the process of flow field flow microfluidic separation device fabrication,the device was fabricated by PDMS-based microfluidic chip standard processing technology.According to the simulation studies,the parameters of the device model were corrected,and the separation between exosomes and BSA components was completed.The results of the normalized research showed that the transit time would be decrease with the increase of the device length and the resolution of each component.Meanwhile,the transit time remained unchanged when the height of the device,and the resolution of each component increased.Besides,there was no significant influence on the resolution and transit time of each component when the width of channel changed.By modifying the particle size of the components,a nonlinear reduction in resolution between the components was obtained.The physical device is fabricated by self-processing method,and the airtightness is strictly analyzed.By improving the fluid overflow of the channel,the fluid in the channel only exists in the channel,which satisfies the requirement of device sealing.In the future study,the biological sample components would be separated by the channel with suitable parameters for the separation operation.This would contribute to the study on exosomes.