压电驱动细胞分选微泵操控机理及设计

The healthcare resources are relatively in shortage in our country, whose root reasons are outdated technology for prevention of diseases spread and its corresponding high expenditures. The Flow Cytometer (FCM), an effective method to diagnose serious diseases in early stage, is very hard to be widely used in remote mountainous areas, fundamental hospitals and clinics, due to its huge volume, complex operation and high cost. The point-of-care testing of biochemical criterion using inertial microfluidic has the merit of high flux and low cost, which is expected to be the supported technology to the ‘first contact care in fundamental hospitals’. However, currently its single flow channel configuration and low function integration result in the low purity quotient of cell sorting. This project integrating design of piezoelectric micro-pumps with convenience of the flow field’s regulation, proposes a novel micro-pump based on piezoelectric driving. And the functions of sample introduction, driving and cell sorting are integrated in this micro-pump. Investigate the law of cells’ motion based on the fluid-structure interaction; reveal the variation rules of flow versus the change of flux, viscosity and the shape of channels’ configuration; explain the interaction mechanism of cells loaded forces in details and dynamic characteristics of cells’ inertial migration. Based on the response characteristics and flow states driving by different excitation signals, a method to cell sorting in high purity quotient is built. Carrying out this project is helpful to improve the technique of point-of-care testing for cells analyses, promote interdiscipline integrating and enhance the level of diagnoses to serious diseases in early stage in our country.

我国医疗卫生资源总量相对不足，其根源是疾病防控技术落后、成本高昂。作为现有重大疾病早期诊断强有力手段的流式细胞仪，却由于体积庞大、操作复杂、成本高等原因，难以在偏远山区、基层医院和诊所推广应用。利用惯性微流控进行细胞分选的生化指标即时检测具有高通量、低成本的优点，可望成为“基层首诊”的重要技术支撑。但现有装置流道构型单一、功能集成度不高，导致操作性差、分选纯度低。本项目结合压电微泵结构设计灵活和流场调控便捷的特点，提出将进样、驱动与细胞分选功能集成，构建压电驱动的细胞分选微泵。研究流固耦合作用下的细胞运动规律，揭示流体随流量、黏度和流道构型的变化规律，阐释细胞受力的相互作用机理，以及细胞惯性迁移动力学特性，根据不同激励信号下流场的响应特征和流动状态，建立高分选纯度的细胞分选方法。本项目的实施有助于推动面向细胞分析应用的即时检测技术的发展，促进学科交叉融合，提升我国对重大疾病的早期诊断水平。

现有的细胞分选用泵多采用注射泵为动力源，从而导致整个系统难以微型化、集成度差，阻碍了细胞分析即时检测技术的发展。本项目提出了一种涡旋流管无阀压电泵来实现液体的传输和微颗粒分选的功能集成。对涡流二极管进行了流场计算和固液两相流分析，得到了流道内微颗粒随流体运动的迁移规律。试验验证了涡旋流管无阀泵的传输性能，及对高粘度液体的待载能力，为构建压电泵的流场参数化控制策略提供了基础。为了避免微泵的粗糙内壁损伤细胞及影响微颗粒的流动轨迹，采用高精度的PμLSE (Projection Micro Litho Stereo Exposure)加工技术进行了微泵制作。对流道的内表面进行了三维形貌扫描，结果表明流道壁面形貌均匀，粗糙度为0.2697µm。当驱动频率为19Hz时，该微泵的输出流量达到最大，为37.44 μL/min。为了增大微泵的输出流量，减少对传输活性颗粒的损伤，提出了柔性仿生瓣膜阀并设计了仿生阀压电泵。试验研究表明，柔性仿生阀的加入，使得压电泵的输出流量增加了170.77%；当传输液体粘度为3.281cP时，压电泵的最大输出流量为1.3 mL/min，最大输出背压为313.7 Pa。针对有阀压电泵的阀体所受应力较大的问题，提出了钹型开槽式截止阀来减小内部阀体所受应力并设计了钹型开槽式阀压电泵。有限元计算结果表明，钹型开槽膜片所受的Von mises应力远小于平板开槽膜片的。为了扩大压电泵的应用领域，建立功能集成型压电泵的设计理论，提出了一种可应用微电子散热领域的非对称型流管分布的无阀压电泵。通过仿真和试验研究，获得了流管直径分布分形维与传热效果间的关联性，并验证了非对称型流管无阀压电泵可实现传热。本项目的实施有助于推动压电泵的发展、扩大其应用领域，并促进各学科间的交叉融合。