微流控芯片的构建及其在细胞拉伸中的应用研究

发布时间：2018-02-01 10:59

本文关键词： 微流控芯片介电电泳介电泳力细胞拉伸应变　出处：《中北大学》2015年硕士论文　论文类型：学位论文

【摘要】：以生物细胞操作技术和微流控芯片分析系统为基础的生物医药研究是当今世界上科技领域中最前沿的科学技术之一。大量证据表明，，细胞的生物力学参数与细胞的生理功能有关系，并且某些疾病的发生和发展是由于细胞的生物力学参数的变化引起的。本文主要研究运用微流控芯片技术和介电电泳技术，在细胞层面上直接对经过相关药物处理后的细胞生物力学性能进行测试，从而实现对新药物的快速评估。运用电场和细胞相互作用产生的介电泳力，将正常细胞和病变细胞进行拉伸，测量其生物力学参数（如应变、泊松比、杨氏模量、弹性常数、粘弹性、粘附力等），然后将病变细胞进行药物处理，再次测量其生物力学参数，将后者获得的参数与前两者进行比较，从而监测药物的药效。将该系统应用于新药研发领域，将进一步加快药物筛选，使得大多数药物在一次研究中尽可能多地获取信息，以提高早期研究效率，增强对药物进入后期阶段的信心，从而大大缩短新药的研发周期。本文的研究重点是：（1）基于介电电泳的细胞拉伸芯片理论基础：偶极矩理论、电介质与相对介电常数、芯片介电电泳的原理、芯片介电电泳的控制因素、球形和椭球形细胞所受介电泳力的计算。（2）用于细胞拉伸的微流控芯片的设计加工：细胞拉伸芯片的设计与仿真；芯片加工材料的选择；PDMS通道的加工工艺；微电极的加工工艺；PDMS通道-玻璃基底键合工艺。（3）运用集成微电极的微流控芯片进行细胞拉伸的实验研究：实验系统的建立；NB4细胞的来源与性质、拉伸NB4细胞的电压和频率选择、拉伸药物处理前后的NB4细胞。（4）细胞拉伸的实验结果与讨论：处理实验数据，得到两种细胞应变值的分布范围，进一步分析两种细胞应变与时间的关系曲线，根据不同时间应变值的差异来检测药物的药效。综上，本文通过自行设计制作的微流控芯片实现对NB4细胞的拉伸操作。重点分析了NB4细胞应变与时间的关系曲线。实验结果表明：药物处理前NB4细胞应变为0.06-0.09，药物处理后NB4细胞的应变为0.18，因此可得出药物处理前的NB4细胞比药物处理后的NB4细胞“硬”。分析应变与时间的关系曲线：两种细胞的应变随时间的增长而增大，药物处理前的NB4细胞的应变较药物处理后的NB4细胞的慢。该数据同样说明了药物处理前的NB4细胞比药物处理后的NB4细胞“硬”，以上实验结果说明，药物对细胞起了一定的作用。
[Abstract]:Biomedical research based on biological cell manipulation technology and microfluidic chip analysis system is one of the most advanced science and technology in the field of science and technology in the world. The biomechanical parameters of the cells are related to the physiological functions of the cells. And the occurrence and development of some diseases are caused by the change of biomechanical parameters of cells. This paper mainly studies the use of microfluidic chip technology and dielectric electrophoretic technology. The biomechanical properties of the cells treated with related drugs were directly tested at the cellular level, so that the rapid evaluation of new drugs could be achieved. The electrophoretic force generated by electric field and cell interaction was used. The biomechanical parameters (such as strain, Poisson's ratio, Young's modulus, elastic constant, viscoelasticity, adhesion force, etc.) of normal and diseased cells were measured. The biomechanical parameters are measured again, and the parameters obtained by the latter are compared with the former, so as to monitor the drug efficacy. The application of the system in the field of new drug research and development will further accelerate drug screening. It allows most drugs to obtain as much information as possible in a single study to improve the efficiency of early research and to increase confidence in the drug's advanced stages. Thus greatly shorten the research and development cycle of new drugs. 1) the basic theory of cell stretch chip based on dielectric electrophoretic: dipole moment theory, dielectric and relative dielectric constant, the principle of chip dielectric electrophoresis, and the controlling factors of chip dielectric electrophoresis. Calculation of the dielectric Electrophoretic Force of spherical and ellipsoidal cells. Design and fabrication of microfluidic chip for cell stretching: design and simulation of cell stretch chip; Selection of chip processing materials; The processing technology of PDMS channel; The processing technology of microelectrode; PDMS channel-glass substrate bonding process. 3) using microfluidic chip integrated microelectrode for cell stretching: the establishment of experimental system; The origin and properties of NB4 cells, the selection of voltage and frequency of stretched NB4 cells, and the NB4 cells before and after drug treatment. (4) the experimental results and discussion of cell stretch: processing the experimental data, the distribution range of the two cell strain values was obtained, and the relationship curve between the two cell strain and time was further analyzed. The efficacy of the drug was measured according to the differences in strain values at different times. In summary, the stretch operation of NB4 cells was realized by microfluidic chip designed by ourselves, and the relationship between strain and time of NB4 cells was analyzed. The results showed that the strain of NB4 cells was 0.06-0.09 before drug treatment and 0.18 after drug treatment. It is concluded that the NB4 cells before and after drug treatment are "hard" than those of NB4 cells after drug treatment. The relationship between strain and time is analyzed: the strain of the two kinds of cells increases with the increase of time. The strain of NB4 cells before drug treatment was slower than that of NB4 cells after drug treatment. The data also showed that NB4 cells before drug treatment were "hard" than NB4 cells after drug treatment. The above results show that the drug has a certain effect on cells.
【学位授予单位】：中北大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：Q2-3;TN492

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