【作者】 刘杰；

【导师】 马希金； 吴江波； 王长娃；

【作者基本信息】 兰州理工大学 ， 动力工程（专业学位）， 2022， 硕士

【摘要】 红细胞的分选和检测技术在血液循环系统疾病的早期诊断、临床治疗和抗病药物研发等医疗领域具有广阔的应用前景。传统的分选及检测方法需借助大型设备,其过程操作复杂、笨重、分选周期长,难以实现临床的快速分选与检测。而确定性侧向位移（Deterministic Lateral Displacement,DLD）技术,具有成本低、坚固耐用的优点,能提供高通量、高分辨率的微粒快速分离。但针对红细胞等非球形的可变形生物微粒在确定性侧向位移芯片中的分选及其运动变形特性研究还不够充分,限制了该技术在实际分选和检测中的应用。因此,本文以DLD为研究平台,围绕红细胞在其中的运动及变形特性展开研究。首先,基于确定性侧向位移基础理论,分析了微流控芯片的结构周期、侧向间隙、微柱几何形貌、流场初始条件对其临界半径的影响;并基于任意拉格朗日欧拉方法构建了流-固耦合模型,模拟刚性粒子（白细胞、血小板）在“工”形阵列中的运动。分析双向耦合作用下粒子与流体间的相互作用及对粒子运动轨迹的影响,为后文研究超弹性红细胞在流场中的运动和变形提供基础依据。其次,基于有限元方法构建了三维红细胞模型,分析红细胞在静力拉伸作用下材料模型的差异对其力学性能的影响,最终选择与实验结果吻合较高的Yeoh材料模型。后续研究中在兼顾红细胞力学性能的同时,为了解决空间大变形导致的网格畸变问题,对红细胞模型进行了简化。并分析了其厚度（垂直面内方向）d_t对力学性能的影响,研究结果表明当d_t=3.91μm时,其变形程度与实验结果基本吻合,该研究为红细胞在剪切流中的形变特性研究提供了基础模型。在此基础上,构建红细胞在微管中运动的流-固耦合模型,分析了剪切流作用下圆管直径、流场初始条件、红细胞的直径及剪切模量对其运动和变形的影响。分别提取红细胞三维和二维模型的变形指数（DI^S）进行对比,结果表明红细胞在剪切流的作用下,二维模型的变形指数DI^S≤0.3也能够较为准确的描述其力学性能。为研究后续红细胞在微柱阵列中的运动,提供了可靠的红细胞应力应变特性。最后,设计了能够有效诱导非球形可变形生物细胞翻滚运动的“工”形微柱阵列,并分析了红细胞在该阵列中的运动轨迹和变形程度。研究结果表明,当“工”形微柱的偏移距离Δλ≤1.5μm时,红细胞以“位移”模式运动;当Δλ≥2μm时,红细胞在流场的作用下呈“之字形”模式运动。进一步改变红细胞的弹性特征,发现当红细胞的剪切模量μ₀≤5.3μN/m时,其在微柱阵列中的运动变形程度较大,无法维持连续稳定的翻滚。表明红细胞在“工”形阵列中的有效分选,需要建立在减小其变形程度的基础上,即红细胞在运动过程中其有效半径应大于临界半径。研究结果可用于更高分离性能的细胞分选芯片结构设计优化,为红细胞的分选通量和精度的提升提供基础依据。更多还原

【Abstract】 The sorting and detection technology of red blood cells has broad application prospects in medical fields such as early diagnosis of blood circulatory diseases,clinical treatment and research and development of anti-disease drugs.The traditional sorting and detection methods require the help of large-scale equipment,which is complicated in operation,cumbersome,and has a long sorting cycle,making it difficult to achieve rapid clinical sorting and detection.The deterministic lateral displacement（Deterministic Lateral Displacement,DLD）technology has the advantages of low cost,robustness and durability,and can provide high-throughput,high-resolution rapid separation of particles.However,the research on the sorting and motion deformation characteristics of non-spherical deformable biological particles such as red blood cells in a deterministic lateral displacement chip is not sufficient,which limits the application of this technology in practical sorting and detection.Therefore,this paper takes DLD as a research platform to study the movement and deformation characteristics of red blood cells in it.Firstly,based on the basic theory of deterministic lateral displacement,the influence of the microfluidic chip’s structural period,lateral gap,micro-column geometry,and initial flow field conditions on its critical radius was analyzed;The pull method constructs a fluid-structure interaction model to simulate the motion of rigid particles（leukocytes,platelets）in an"I"-shaped array.The interaction between the particle and the fluid under the two-way coupling and the influence on the particle’s trajectory are analyzed,which provides a basis for the later study of the motion and deformation of hyperelastic red blood cells in the flow field.Secondly,a three-dimensional red blood cell model was constructed based on the finite element method,and the influence of the difference of the material model of red blood cells on its mechanical properties under static tension was analyzed,and the Yeoh material model that was in good agreement with the experimental results was finally selected.In the follow-up research,while taking into account the mechanical properties of red blood cells,in order to solve the problem of grid distortion caused by large spatial deformation,the red blood cell model was simplified.And analyzed the influence of its thickness（vertical in-plane direction）d_t on the mechanical properties,the results show that when the thickness is d_t=3.91μm,the deformation degree is basically consistent with the experimental results,this research provides a basis for the research on the deformation characteristics of red blood cells in shear flow Model.On this basis,a fluid-structure interaction model of red blood cells moving in microtubules is constructed,and the effects of the diameter of the circular tube,the initial conditions of the flow field,the diameter of red blood cells and the shear modulus on its movement and deformation under the action of shear flow are analyzed..The deformation index （DI^S） of the three-dimensional and two-dimensional models of red blood cells was extracted for comparison.The results showed that the deformation index of the two-dimensional model of DI^S≤0.3could accurately describe the mechanical properties of red blood cells under the action of shear flow.Reliable erythrocyte stress-strain properties are provided for the study of subsequent erythrocyte movement in the micropillar array.Finally,an"I"-shaped micropillar array that can effectively induce the rolling motion of non-spherical deformable biological cells is designed,and the movement trajectory and deformation degree of red blood cells in the array are analyzed.The research results show that when the offset distance of the"I"-shaped micro-column isΔλ≤1.5μm,the red blood cells move in a"displacement"mode;when it isΔλ≥2μm,the red blood cells move in a"zigzag"mode under the action of the flow field.To further change the elastic characteristics of red blood cells,it was found that when the shear modulus of red blood cells wasμ₀≤5.3μN/m,their motion deformation in the micro-pillar array was large,and the continuous and stable rolling could not be maintained,indicating that the red blood cells were effectively divided in the"I"-shaped array.The selection should be based on reducing the degree of deformation,that is,the effective radius of red blood cells should be greater than the critical radius during the movement.The research results can be used to optimize the structure design of cell sorting chips with higher separation performance,and provide a basis for the improvement of red blood cell sorting throughput and precision.更多还原