| Early detection and diagnosis of tumor cells is of vital importance for guiding the clinical treatment of cancer.However,the number of tumor cells is extremely rare,and they are free in complex environments such as blood and are in the background of a large number of impurity cells.Therefore,the separation and enrichment of tumor cells with high recovery rate and high purity is the basis and prerequisite for cancer research and analysis,and even a variety of biological,biomedical and clinical diagnostic research.Based on the review of cell sorting methods based on microfluidic technology,this article focuses on deterministic lateral displacement cell sorting technology,focusing on sorting mechanism,sorting structure morphology optimization,chip preparation technology,sorting performance test Performing theoretical and experimental research on the integration of the characterization and sample solution dilution process,a tumor cell sorting chip is proposed,which has made a certain breakthrough in the high recovery rate and high purity of tumor cell sorting.The specific research work of this article is as follows:1)A morphology optimization method based on parameterized curves is proposed to optimize the morphology of the cross section of the sorting function micropillar in the deterministic lateral displacement technology.Starting from the separation principle,it is proposed to control the flow velocity distribution in the micro-column gap as the key point.Based on the third-order Bezier curve fitting the initial circular crosssectional shape,the configuration is adjusted by scaling the control point coordinates of the curve,with the goal of reducing the critical radius and controlling the flow velocity distribution in the gap,and keeping the convex structure as a constraint.Construct a parameterized morphology optimization problem.The solution is based on the Nelder-Mead method,and the cross-sectional morphology of the drop-shaped micro-columns with a smaller critical radius and fewer low-velocity regions is obtained.2)A fluid-structure coupling model is constructed based on the arbitrary Lagrangian-Euler method.Considering the two-way coupling effect of particles and fluid in the flow field,the analysis of the influence of the flow field parameters on the particle trajectory is improved compared with the numerical simulation method that uses particles as particles to participate in the flow.Use Lagrangian description to track particle motion and deformation,use Euler description to update key parameters of the flow field,and couple equations at the boundary of fluid and solid.In this way,numerical simulation of the particle trajectory in the circular cross-section and dropshaped cross-section micro-pillar array is carried out.Analyzing the control parameters such as flow rate and size,and the influence of adsorption and collision on the separation,it is proposed that the compression of the particles on the fluid in the gap leads to an increase in the relative critical radius.3)Reveal the mechanism of polymer material PMMA and epoxy resin packaging failure from the perspective of theory and experiment,and propose a microfluidic chip packaging process based on surface modification and pretreatment.Aiming at the cracking and warping phenomenon of PMMA chips after laser processing in solvent bonding,parylene film evaporation process and thermal annealing process were proposed to realize bonding.Aiming at the failure phenomenon of the molten prepolymer blocking the chip channel in the thermal diffusion method of epoxy resin chip bonding,a local hydrophobic treatment process based on photolithography technology is proposed to realize chip packaging and enhance the packaging effect;4)Develop a deterministic lateral displacement sorting chip based on drop-shaped cross-section micro-columns,which is used to sort polystyrene particles,prostate cancer cells,and gastric cancer cells.The effect of flow rate on the sorting effect was studied.The sorting recovery rate of 15μm particles under 300μL/min flow rate was 98.4%,and the purity was 97.8%.On the background of blood cells,the average recovery rate of prostate cancer cell sorting was 93.81%,and the average separation purity was 90.35%;the average recovery rate of gastric cancer cell sorting was 84.58%,and the average separation purity was 91.95%.It proved that the chip is effective for tumor cells with high-precision and high-purity sorting performance.5)In order to further carry out efficient automatic dilution and mixing of the sample mixture in the pretreatment process,the principle and method of the active mixing device on the microfluidic chip were studied.A design method of active electroosmotic micromixer is proposed.Based on the optimal control method,the Dirichlet boundary control problem is constructed,and the optimal distribution of the electrodes of the electroosmotic micromixer on the sidewall of the channel is solved in reverse to achieve the best mixing performance.The mixing measure function that characterizes the mixing effect is 0.025,which is better than the set threshold of 0.050,which proves the effectiveness of the design method. |
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