微流体隔离泵送和微流体次序流动系统研究

发布时间：2018-06-25 18:43

本文选题：微流体通用平台 + 气泡　；参考：《哈尔滨工业大学》2015年博士论文

【摘要】：微观尺度下的高传热传质效率和低物质能量消耗使微流体技术在疾病即时诊断和环境监测等领域具有巨大应用潜力,但目前微流体技术还无法很好的解决液体次序流动芯片及平台的通用性和可控性差、容易出现气泡等问题。本论文针对微流体分子诊断(Microfluidic molecular diagnostic)中的液体次序流动和控制提出一种新型微流体负压驱动泵送技术,研究一种新型核酸与蛋白质测定次序流动控制通用平台,实现不同形式的多样本、多过程的流体泵送控制,从而促进和推动微流体疾病即时诊断相关产品的成熟化。由聚二甲基硅氧烷(Polydimethylsiloxane,PDMS)材料制作的微流体芯片,通过负压驱动进行泵送时易产生影响微流体芯片正常功能的无用空气气泡。本文研究负压流动中PDMS流道内无用气泡生成和长大机理,基于PDMS的表面斥水性和流道结构特性,提出在流道内不同位置生成气泡的物理模型,并建立考虑多相间物质传递和压力变化的多物理场耦合数学模型,对气泡在形成后的体积变化过程进行数值仿真分析和实验验证,对气泡变化过程中气泡长大速率特性进行分析,研究气泡平均变化速率与关键影响参数之间的关系。在微流道内气泡产生和变化机理研究基础上,本论文提出一种负压驱动的微流体液体隔离泵送技术。利用PDMS材料的选择透过特性,将被泵送液体与负压驱动气源隔离,依靠通道之间空气扩散引起的流道压力变化进行液体泵送,从根本上避免了液体流动时流道内无用气泡的形成,并且实现了封闭流道结构内的液体泵送。本文对该微泵技术的液体流动过程进行数学模型的研究和仿真计算对比,分析关键过程特性和设计参数;对该微泵技术进行实验研究,得出液体泵送速率与设计参数之间的定量关系;为扩大应用领域,在该微泵上集成手指薄膜泵,开发可以脱离外部能源支持、进行独立操作的微流体泵送技术。处于同一平面的液体流道与负压气体通道之间无法实现相互交叉的立体结构关系,无法集成多层结构的控制模块。本文提出多层复合结构液体隔离泵送技术,采用热塑塑料和硅胶薄膜等材料,将液体流道和气体流道分别置于不同平面结构上,两者之间通过透气硅胶薄膜隔离,并在片上集成微阀等立体控制结构。本文对复合结构芯片的快速、低成本制备方法进行研究,在更短的时间内将芯片设计转化制备成为复合结构微流体芯片,提高测试和优化效率。本文设计具有无气泡、高可控性、通用性、自动化等特点的微流体次序流动与控制平台,并对不同类型的微流体次序流动芯片进行研究。本文在复合结构微流体芯片上集成一定数目的气动薄膜微阀,使负压驱动气体同时对液体泵送和回路控制进行操作,在此基础上分别对三种面向核酸测定的离散化次序流动芯片以及面向蛋白质测定的次序流动芯片的结构、工作原理和流动特性进行研究。本文对可编程的微型气动系统进行设计和测试,并配合次序流动芯片对自动化、多样本、多试剂、多步骤的微流体次序流动控制平台进行实验研究。
[Abstract]:Microscale Gao Chuanre mass transfer efficiency and low energy consumption make microfluidic technology have great potential in the field of real-time diagnosis of disease and environmental monitoring. But at present, microfluidic technology can not solve the problems of liquid order flow chip and the poor controllability of the platform, easy to appear bubbles and so on. A new type of microfluidic negative pressure driving pump technology is proposed for liquid sequence flow and control in Microfluidic molecular diagnostic. A new type of common platform for sequencing flow control for nucleic acid and protein determination is studied. A micro fluid chip made of Polydimethylsiloxane (Polydimethylsiloxane, PDMS) material, which is made by the material of poly (methyl siloxane) (PDMS), can easily produce unused air bubbles that affect the normal function of microfluidic chips by negative pressure driving. This paper investigates the formation of unused bubbles in the PDMS flow channel in negative pressure flow and The growth mechanism, based on the surface water repellency and channel structure characteristics of PDMS, presents a physical model for the formation of bubbles at different locations in the flow channel, and establishes a multi physical field coupling mathematical model considering the multiphase material transfer and pressure change, and carries out numerical simulation analysis and experimental verification on the volume change over the bubble after the formation of the bubble. The relationship between the average change rate of bubble and the key parameters in the change process is analyzed. On the basis of the study on the mechanism of bubble generation and change in the micro channel, a negative pressure driven micro fluid liquid isolation pump technology is proposed in this paper. The selection of the PDMS material will be pumped by the pump. The liquid and the negative pressure drive gas source isolation, depending on the flow channel pressure change caused by the air diffusion between the channels to carry out the liquid pump, which fundamentally avoids the formation of the useless bubbles in the flow passage of the liquid flow, and realizes the liquid pump in the closed flow channel structure. Compared with the simulation calculation, the characteristics of the key process and the design parameters are analyzed. The quantitative relationship between the liquid pump rate and the design parameters is obtained by the experimental study of the micro pump technology. In order to expand the application field, the finger film pump is integrated on the micro pump, and the micro fluid pump technology can be independently operated from the external energy support to carry out the independent operation. The relationship between the liquid channel and the negative pressure gas channel in the same plane can not be realized, and the control module of multilayer structure can not be integrated. In this paper, the multi-layer composite structure liquid isolation pump technology is put forward. The liquid channel and the gas channel are put in different leveling of the liquid channel and the gas channel, respectively. In the surface structure, the two kinds of stereoscopic control structures are separated by air permeable silica gel film, and micro valves are integrated on the chip. In this paper, the fast and low cost preparation methods of the composite structure chip are studied. In a short time, the chip design is transformed into a composite structure microchip to improve the testing and optimization efficiency. A micro fluid sequence flow and control platform with no bubbles, high controllability, versatility, automation and other characteristics, and the study of different types of microfluidic sequence flow chips. This paper integrates a certain number of pneumatic thin film microvalves on a composite microchip to make the negative pressure driven gas simultaneously pump and loop control of the liquid. On this basis, three discrete sequence flow chips for nucleic acid determination and the structure, working principle and flow characteristics of the sequence flow chip for protein determination are studied. The programmable micro pneumatic system is designed and tested in this paper, and the sequence flow chip is combined with automation, diversity, and more. Reagents, multi-step microfluidic order flow control platform are studied.
【学位授予单位】：哈尔滨工业大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R318;TN405

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