Construction And Application Of Heterogeneous Gel Particles Based On Microfluidic Technology

The manufacture of heterogeneous gel particles with special internal microstructures has attracted wide interest in the fields of self-assembly,drug delivery,tissue engineering,and multi-channel detection.The advantage of heterogeneous gel particles is that different regions in a droplet can be used as payload to encapsulate complex materials for performing complex functions at the level of a single droplet.In recent years,the manufacturing methods of heterogeneous gel particles have been extensively explored and developed,such as flow lithography,electrostatic injection technology and microfluidic assistance.However,these methods are largely limited by the application of biocompatibility and the complexity of particle structure.The complex microstructure requires strict manipulation of microfluidics to achieve fine adjustment and fixation of the internal structure of particles.Currently,the published particle structures are usually limited to less than ten different functional load packages,and often involve the use of non biocompatibility such as electricity,ultraviolet light,surfactant,high ionic strength solution,etc.Therefore,it is of great significance to develop more compatible manufacturing methods for potential biological applicationsIn this paper,based on microfluidic technology,the idea of threedimensional microfluidic droplet manufacturing is proposed,in order to break through the limitation of traditional particle internal complex partition.The goal of free expansion of particle internal partition has been realized.The application examples of multifunctional particles are proposed,including cell culture,intelligent particle manipulation and multiple analysis.The research contents are as follows1.In order to realize the fabrication of ultra-high degree of freedom multicompartment particles,we propose a microfluidic assembly method based on microfluidic chip and capillary device to realize the three-dimensional manipulation of microfluidic.The ingenious microfluidic chip design allows the multicompartment sodium alginate gel particles to have adjustable internal microstructures.By controlling the capillary device,we can control the particle geometry.In addition,by adjusting the micro structure of the chip,capillary diameter,gap length between the two kinds of microfluidic components,flow rate and other droplet manufacturing parameters,the corresponding design of particle size,the number or proportion of different areas in the particle can be widely changed according to the needs.By ingenious design,the planar divergent multiphase flow can be mapped to the three-dimensional structure of particles to form multicompartment microspheres.As a convincing evidence,the construction of dual-,six-,ten-and twenty-compartment microspheres were successfully obtained.These results show that this method can be used as a new method of anisotropic particle manufacturing.2.In order to achieve green,simple and high-throughput batch production of heterogeneous gel microspheres and to meet widely applied in bioengineering and basic medical research.we designed a microfluidic assisted gas shearing droplet generator to customize highly developed heterogeneous gel particles,which do not damage or change the properties and activity of the encapsulated materials inside the gel.The droplet manufacturing device consists of two parts:the upstream component is equipped with a multi structure microfluidic chip,which is used to adjust the laminar flow pattern in the channel;The downstream component is a gas shearing device,and nitrogen is selected as the driving force to achieve droplet rupture.It can realize the free control of the internal microstructure of hydrogel particles,and the droplet manufacturing parameters such as particle size and manufacturing frequency can also be actively controlled,with a high degree of freedom.It is worth mentioning that this method does not involve the non biocompatible operations such as electricity,ultraviolet light,surfactant and high ionic strength solution,showing advantages in the field of biological application of droplets.3.The multifunctional cell platform of heterogel microparticles on single particle level was constructed.This work,based on a multi-compartmental particle template,prepared hydrogel particles containing six similar compartments,which do not interfere with each other but allow small molecule patterns to communicate.The fluorescent nanomaterials,magnetic particles,hepatoma cells and endothelial cells were co encapsulated to construct an in vitro liver organ model.This model integrates the functions of space recognition and intelligent control in the particles.Because all the materials are biocompatible,the cells can be co-cultured in three dimensions without invasion and damage markers,which is beneficial to monitor the life behavior of each cell in vitro.4.A multiple analysis model based on multicompartmental particles is proposed.Firstly,different DNA probes were loaded in multiple compartments of the multicompartment microstructure by microfluidic encapsulation.The boundaries of these regions were obvious and sharp without crosstalk.The reliability of the method is verified by comparing the analysis results of different DNA probe combinations.Because of the high scalability of multicompartmental particles,it can simply increase the number of compartments to increase the number of probe loads.Therefore,this method is of great significance for real-time monitoring,how multiple analysis and other fields.