Three-dimensional Assembly Of Cells Based On Robotic Micromanipulation Combined With Magnetic Guidance

Human daily life is filled with unpredictable natural disaster and behavioral accident that may cause tissue damage and organ loss,and human health is threatened by aging and degeneration of tissue and organ.The tissue engineering is developing three-dimensional(3D)cell assembly method to construct artificial tissue with functions of human organ,and it provides a new way for organ repair and regeneration.However,the current vascularization of artificial tissue is low,which may result in a lack of effective nutrient supply in the culture process.To avoid the generation of gangrene in 3D artificial tissue,researchers have widely used multilayer porous cell scaffold as a microenvironment for cell metabolism.However,the conventional construction method of this scaffold requires complicated peripheral equipment and high production cost,which is not conducive to popularization and application of the scaffold.To solve the above problem,this study proposes a new method that integrates robotics,microfluidics and magnetic guidance to effectively simplify the construction process of multilayer porous cell scaffold orderly assembled by cell microcarrier in the liquid phase environment.The main research issues and results are described in this paper as follows.Firstly,aiming at the requirement of ordered arrangement of the cell microcarrier in multilayer porous cell scaffold,a 3D assembly method of cells based on robotic micromanipulation combined with magnetic guidance is proposed.The 3D construction of multilayer porous cell scaffold in a liquid phase environment is achieved through setting up a magnetically-guided micromanipulation robot system;the accuracy,flexibility and efficiency of in-vitro construction of artificial tissue are improved based on fusion of micromanipulator,magnetically-guided device and visual feedback.Secondly,in view of the poor controllability of the cell microcarrier,the magnetic fibrous cell microcarrier with adjustable size is developed by using microfluidic spinning method.The microfluidic chip is developed with the soft lithography;the superparamagnetic magnetic nanoparticle is synthesized by using chemical co-precipitation method;the corresponding relationship between the volumetric flow rate of relevant solution and the width of the magnetic fibrous cell microcarrier is analyzed;the on-chip processing of magnetic fibrous cell microcarrier is realized;the magnetic response mechanism of the cell microcarrier is analyzed;the rapid magnetic response characteristic of the cell microcarrier is increased with the help of magnetic nanoparticle.Next,in order to solve the problem that magnetic fibrous cell microcarrier is difficult to be flexibly micromanipulated in the magnetic field generated by permanent magnet,this paper proposes a method to form the dot-matrix magnetic flux density by utilizing aggregation and discretization of the magnetic flux density.The optimal placement area of the magnetized device is selected through theoretical analysis;the parameters of the magnetized device are optimized according to simulation analysis;the dot-matrix magnetic flux density is formed by the soft magnetic iron wire with magnetic effect and array layout;the magnetic field distribution of the permanent magnet is changed with the magnetized device;magnetic fibrous cell microcarrier is diversified micromanipulated by using magnetic guidance in the liquid phase environment.Then,to overcome the problems of low efficiency of manual operation,difficultly positioning of cell layout,lack of internal nutrient supply and large influence of fluid disturbance,this paper orderly constructs the multilayer porous cell scaffold by using robotic micromanipulation combined with magnetic guidance in the liquid phase environment.The principle of automatic microassembly of the robotic system is analyzed;the automatic identification of the soft magnetic iron wire inside the magnetically-guided device and the automatic tracking of the magnetic fibrous cell microcarrier are completed;the automated assembly strategy for magnetic fibrous cell microcarrier is designed;the ordered construction of the multilayer porous cell scaffold with high porosity is realized.Finally,the effectiveness of the 3D cell assembly method proposed in this study is verified by experiments.The cell adhesion of the magnetic fibrous cell microcarrier is studied;the 3D cell assembly based on the multilayer porous cell scaffold is initially achieved.This method provides a new theory for tissue repair and organ replacement,and it also establishes a new model for drug development and toxicity testing.