本文關(guān)鍵詞： 微流控芯片 介電電泳 介電泳力 細(xì)胞拉伸 應(yīng)變　出處：《中北大學(xué)》2015年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：以生物細(xì)胞操作技術(shù)和微流控芯片分析系統(tǒng)為基礎(chǔ)的生物醫(yī)藥研究是當(dāng)今世界上科技領(lǐng)域中最前沿的科學(xué)技術(shù)之一。大量證據(jù)表明，，細(xì)胞的生物力學(xué)參數(shù)與細(xì)胞的生理功能有關(guān)系，并且某些疾病的發(fā)生和發(fā)展是由于細(xì)胞的生物力學(xué)參數(shù)的變化引起的。本文主要研究運(yùn)用微流控芯片技術(shù)和介電電泳技術(shù)，在細(xì)胞層面上直接對(duì)經(jīng)過(guò)相關(guān)藥物處理后的細(xì)胞生物力學(xué)性能進(jìn)行測(cè)試，從而實(shí)現(xiàn)對(duì)新藥物的快速評(píng)估。運(yùn)用電場(chǎng)和細(xì)胞相互作用產(chǎn)生的介電泳力，將正常細(xì)胞和病變細(xì)胞進(jìn)行拉伸，測(cè)量其生物力學(xué)參數(shù)（如應(yīng)變、泊松比、楊氏模量、彈性常數(shù)、粘彈性、粘附力等），然后將病變細(xì)胞進(jìn)行藥物處理，再次測(cè)量其生物力學(xué)參數(shù)，將后者獲得的參數(shù)與前兩者進(jìn)行比較，從而監(jiān)測(cè)藥物的藥效。將該系統(tǒng)應(yīng)用于新藥研發(fā)領(lǐng)域，將進(jìn)一步加快藥物篩選，使得大多數(shù)藥物在一次研究中盡可能多地獲取信息，以提高早期研究效率，增強(qiáng)對(duì)藥物進(jìn)入后期階段的信心，從而大大縮短新藥的研發(fā)周期。本文的研究重點(diǎn)是： （1）基于介電電泳的細(xì)胞拉伸芯片理論基礎(chǔ)：偶極矩理論、電介質(zhì)與相對(duì)介電常數(shù)、芯片介電電泳的原理、芯片介電電泳的控制因素、球形和橢球形細(xì)胞所受介電泳力的計(jì)算。 （2）用于細(xì)胞拉伸的微流控芯片的設(shè)計(jì)加工：細(xì)胞拉伸芯片的設(shè)計(jì)與仿真；芯片加工材料的選擇；PDMS通道的加工工藝；微電極的加工工藝；PDMS通道-玻璃基底鍵合工藝。 （3）運(yùn)用集成微電極的微流控芯片進(jìn)行細(xì)胞拉伸的實(shí)驗(yàn)研究：實(shí)驗(yàn)系統(tǒng)的建立；NB4細(xì)胞的來(lái)源與性質(zhì)、拉伸NB4細(xì)胞的電壓和頻率選擇、拉伸藥物處理前后的NB4細(xì)胞。 （4）細(xì)胞拉伸的實(shí)驗(yàn)結(jié)果與討論：處理實(shí)驗(yàn)數(shù)據(jù)，得到兩種細(xì)胞應(yīng)變值的分布范圍，進(jìn)一步分析兩種細(xì)胞應(yīng)變與時(shí)間的關(guān)系曲線，根據(jù)不同時(shí)間應(yīng)變值的差異來(lái)檢測(cè)藥物的藥效。 綜上，本文通過(guò)自行設(shè)計(jì)制作的微流控芯片實(shí)現(xiàn)對(duì)NB4細(xì)胞的拉伸操作。重點(diǎn)分析了NB4細(xì)胞應(yīng)變與時(shí)間的關(guān)系曲線。 實(shí)驗(yàn)結(jié)果表明：藥物處理前NB4細(xì)胞應(yīng)變?yōu)?.06-0.09，藥物處理后NB4細(xì)胞的應(yīng)變?yōu)?.18，因此可得出藥物處理前的NB4細(xì)胞比藥物處理后的NB4細(xì)胞“硬”。分析應(yīng)變與時(shí)間的關(guān)系曲線：兩種細(xì)胞的應(yīng)變隨時(shí)間的增長(zhǎng)而增大，藥物處理前的NB4細(xì)胞的應(yīng)變較藥物處理后的NB4細(xì)胞的慢。該數(shù)據(jù)同樣說(shuō)明了藥物處理前的NB4細(xì)胞比藥物處理后的NB4細(xì)胞“硬”，以上實(shí)驗(yàn)結(jié)果說(shuō)明，藥物對(duì)細(xì)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.
【學(xué)位授予單位】：中北大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類(lèi)號(hào)】：Q2-3;TN492

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