【作者】 李经民；

【导师】 刘冲；

【作者基本信息】 大连理工大学 ， 微机电工程， 2010， 博士

【摘要】 本文将具有“立体通道结构”或“多层结构”的微流控器件称为立体结构微流控器件。立体通道结构是指微通道内部具有立体微结构,多层结构是指在一般双层结构的基础上增加器件层数。立体结构微流控器件将多种功能单元集成到一起,可以实现分层、分区域的样品操控。对立体结构微流控器件的研究为实现μ-TAS系统集成化、微型化提供了基础。例如,在进行细胞分析时,可以在第一层上利用通道内立体微坝和微柱阵列进行细胞筛选,筛选出的细胞在第二层上利用通道内微陷阱阵列进行单细胞捕捉,然后在第三层上进行细胞裂解,在第四层上进行PCR扩增,使全部细胞分析过程可以在同一器件上快速完成。热塑性聚合物是制作立体结构微流控器件的重要材料之一,热塑性聚合物立体结构微流控器件可以实现批量化制造,对于μ-TAS系统的的未来发展具有重要意义。然而,目前对于热塑性聚合物立体结构微流控器件的研究还存在较多问题：(1)立体结构微通道热压中聚合物形变填充机理研究不足；(2)热键合过程中微通道变形严重,没有理论模型可以对通道变形机理进行分析；(3)热键合中片上集成电极容易产生断裂,目前没有可以揭示断裂机理的理论模型；(4)多层芯片封合方法欠缺。本文依托“973”国家重点基础研究发展计划“高性能微流控芯片／器件的制备方法及相关理论”(NO.2007CB714502)和国家自然科学基金重大项目“仿生—微纳流控芯片系统的研究”(NO.20890024),针对上述问题进行了如下研究：(1)对玻璃态／高弹态聚合物在热压中的粘塑性和高弹性力学行为进行了研究,为立体微结构热压奠定了基础。通过理论分析、数值模拟、热压过程实验拍摄和微结构成形分阶段热压实验,研究了热压中热塑性聚合物的形变填充机理。提出了“欠填充区域”的概念,并研究了“欠填充”的产生和消除机理,建立了热压过程中的加温速率、加载速率和保温保压时间等工艺参数与“欠填充”区域面积的关系。在本部分内容中,对于“玻璃态或高弹态热塑性聚合物”在凸模热压中形变填充行为的研究具有新颖性,特别是对“欠填充”机理进行的研究具有创新性,之前未见报道。(2)建立了热塑性聚合物毛细管电泳芯片集成电极在热键合中的受力模型,提出了新型低结晶度PET毛细管电泳芯片的微通道热压工艺、电极对准工艺和低温低压键合工艺。基于粘弹性理论和断裂理论,建立了热键合中电极的受力模型,对电极应力与键合工艺参数、热应力以及电极跨距之间的关系进行了分析,并通过有限元模拟和热键合实验对分析结果进行了验证。研究了新型低结晶度PET毛细管电泳芯片的制作方法,对其中的储液池激光加工、微通道热压、片上集成电极对准、材料表面改性和芯片键合等问题进行了研究。本部分内容中,对于“片上集成电极受力模型”和“PET毛细管电泳芯片微通道热压工艺、电极对准工艺和低温低压键合工艺”的研究具有创新性,相关研究之前未见报道。(3)研究了热键合中微通道的变形机理,使用“预补偿法”减小微通道变形对通道内立体微结构的影响,制作了带有通道内立体微堰的PMMA血细胞筛选微流控器件。基于热粘弹性理论,对热键合中微通道的变形进行了理论分析、有限元仿真和实验研究。针对变形会导致通道内微结构失效的问题,提出了“预补偿法”。制作了带有通道内微堰结构的血细胞筛选立体微流控器件,对其中的预补偿量的确定、通道网络结构设计、硅模具的制作、立体微通道热压和芯片键合等问题进行了研究。本部分内容中,对于“热键合中微通道变形机理和变形量模型”、“微通道变形预补偿”以及“带有通道内微堰结构的PMMA细胞筛选微流控器件制作方法”的研究具有创新性,相关研究之前未见报道。(4)提出了热塑性聚合物多层立体结构微流控器件的制作方法。通过数值模拟和多层器件键合实验,研究了储液池直径、通道宽度和基片厚度等因素对多层键合的影响。提出了热塑性聚合物多层器件键合法——MTBP法。对MTBP法所包含的多层异厚键合工艺(DTSLB)、传力镶块辅助键合工艺(EBAB)、多层器件分步键合工艺(MSB)、热塑性聚合物基片表面改性工艺(TP-SM)和器件激光切边(LEW)等进行了研究。使用MTBP法,本文制作了三种具有立体通道网络结构的PMMA多层微流控器件,并成功用于试剂混合。在本部分内容中,MTBP法及其所包含的EBAB、MSB、DTSLB、LEW均为首次提出,而TP-SM是对已有技术改进得到的工艺。更多还原

【Abstract】 In this study, we call microfluidic devices which have three-dimensional channels or multilayer structures as "three-dimensional microfluidic devices". Among which, three-dimensional channels mean certain inner microstructures exist in the channels, and multilayer structures mean the device composes by more than two layers.In planar microchip, when the chip is used for cells filtration and trapping, especial electric or magnetic fields are required. However, three-dimensional devices can do these only by using the microstructures fabricated in microchannels, which is simple and quick. The development of three-dimensional microfluidic devices have become a hot topic.Sample operation is achieved only in a planar channel for double layer microfluidic chip, which is one of the bottlenecks slowing the realization of trueμTAS platforms. An approach to overcome this problem is the fabrication of multilayer microfluidic systems, in which each layer can achieve a function. The development of multilayer microfluidic devices have become a forefront topic.Hot embossing and thermal bonding, which are significant approaches to fabricate thermoplastic planar microfluidic device, have difficulties in the fabrication of multilayer microfluidic devices:(1) the replication precision is not acceptable, and the replication defects can easily generate; (2) channel deformation can destroy the in-channel structures; (3) multilayer bonding is affected by reservoir diameter, channel width and substrate thickness.The work is supported by National Basic Research Program of China (2007CB714502) and Major Program of National Natural Science Foundation of China (20890024). It emphasizes on the theory and fabrication of three-dimensional microfluidic devices with hot embossing and thermal bonding, the research works can be summarized as follows:(1) The filling and deformation behavior of glassy or hyperelastic thermoplastics is studied. This work lays a foundation for the embossing of three-dimensional microstructures.The filling and deformation behavior during hot embossing is studied based on theoretical analysis, finite element simulation, synchronous recording and asynchronous analysis. We present the conception of "lack-filling region", and study its formation and elimination. The relationship between lack-filling area and heating rate, applying pressure rate and remaining temperature and pressure time has been established.The study of filling and deformation behavior of glassy or hyperelastic thermoplastics during hot embossing with male die have not been reported. (2) The fracture mechanism of metal electrodes integrated on thermoplastic electrophoresis microchips is studied. Fabrication approach for a new kind of PET electrophoresis microchip is developed.The relationship between electrode stress and bonding parameters, thermal stress and the length of electrode in reservoir is studied base on fracture theory and visco-elastic theory. Bonding experiments and finite element analysis are conducted to verify the theoretical results. Fabrication approach of PET microchips is developed, and the fabrication of reservoir, the hot embossing of microchannels, the alignment of electrode, surface modification and thermal bonding process are studied.In this section, the studies of electrode fracture mechanism and fabrication approach for PET electrophoresis microchips are innovative.(3) The deformation mechanism of microchannel during thermal bonding is studied. An approach, named pre-compensation, is presented to minimize the effects of channel deformation on in-channel microstructures. Fabrication approach of PMMA blood cells filtration device with in-channel microweirs is developed.Based on thermal visco-elastic theory, the channel deformation during thermal bonding is studied by theory and simulation. The theoretical results are verified by experiments. Pre-compensation approach is presented to minimize the effects of channel deformation. Fabrication approach of blood cells filtration device with in-channel microweirs is developed. The compensation value, channel network design, silicon mold fabrication, three-dimensional channel embossing and chip bonding are investigated.In this section, the studies of channel deformation model, channel pre-compensation and fabrication approach for PMMA blood cells filtration are innovative.(4) An approach for the fabrication of multilayer three-dimensional thermoplastic microfluidic device is presented.Relationship between reservoir diameter, channel width, substrate thickness and multilayer bonding is established through finite element simulation and multilayer bonding experiments. A new approach for multilayer thermoplastic microdevices bonding is presented. The processes included in MTBP, such as DTSLB, EBAB, MSB, TP-SM and LEW are studied. Three multilayer PMMA microfluidic devices are fabricated using MTBP.In this section, EBAB, MSB, DTSLB and LEW approaches are all presented for the first time. TP-SM is an improved approach.更多还原