Research On Manipulation Of Concentration Micro-droplet Microfluidic Chips For Drug Microspheres

In the drug delivery system,drug microspheres have attracted more and more attention due to their good drug loading and controlled release properties.The most important factor that affects the performance of a drug microsphere is the concentration of the drug packaged by the microsphere and the particle size of the microsphere.In addition,they also have a great impact on the way of administration.The traditional micro-droplet chip can be used to prepare microdroplets with uniform and adjustable size,but for micro-droplets with multiple concentrations,micro-mixing must be performed after the micro-droplets are generated.Such micro-mixing requires a certain micro-mixing structure or external force.It will cause the breakage and splitting of the micro-droplets,and the insufficient mixing effect will cause a large amount of drug loss after the cross-linking reaction.This paper proposes a concentration micro-droplet chip for drug microspheres.The chip can stably realize the concentration gradient distribution of the drug first,then generate the concentration-gradient micro-droplets,and finally realize the drug gel micro-droplet through the cross-linking reaction.The preparation of the spheres can realize the preparation of multi-concentration and controllable particle size drug microspheres,which provides a more reliable solution for studying the optimal concentration and particle size of drug sustained-release gel microspheres.The main research work of this paper is as follows:First,according to the requirements of preparing drug microspheres and summarizing the related theories,concentration gradient and droplet formation mechanism of microfluidic chips,the structure and flow channel of concentration microdroplets are designed.The flow channel design of the concentration microdroplet chip is divided into two parts: the first part is the mixing of the drug and the sodium alginate solution to form a mixed solution containing different drug concentrations and sodium alginate,the second part is the sodium alginate solution containing different concentrations of the drug The mineral oil of the surfactant forms droplets at the T-shaped structure.Through the above two parts,droplets of sodium alginate with different concentrations of drugs are formed.In the design process,in order to improve the mixing efficiency,the tree-shaped concentration structure was optimized to a surrounding concentration structure,and the T-shaped structure outlet flow channel was reduced by 100 μm to produce smaller droplets.Secondly,through the coupled simulation of the transfer of dilute substances and the phase field method of two-phase flow in the COMSOL Multiphysics software,the simulation and simulation generate the concentration of micro-droplets by setting the conditions of the simulation module.The simulation results show that micro-droplets of a set concentration can be generated,and the size of the generated droplets can be controlled by adjusting the flow rate of the oil phase inlet.The injection molding method is again used to prepare the concentration micro-droplet chips,where the chip male mold used in the injection molding method is made by light-curing3 D printing technology.The preparation material of the concentrated micro-droplet chip adopts PDMS with good biocompatibility,and after injection molding,the substrate and cover sheet are bonded by a thermal bonding method.Finally,the observation of the experiment on the concentration microdroplet chip was carried out,and it was verified that the chip flow channel can produce the set concentration droplet,and the size of the generated microdroplet was controlled by changing the oil phase flow rate.Then the microdroplets and calcium chloride solution were cross-linked to form sodium alginate drug gel microspheres.The microspheres were characterized by an inverted fluorescence microscope.Finally,the observation and analysis of the internal drug packaging of the drug gel microspheres verified that the drug gel microspheres prepared by the concentration microdroplet chip can well achieve the packaging of different concentrations of drugs,which can meet the requirements of biopharmaceuticals.