細(xì)胞在形態(tài)學(xué)、增殖和對(duì)外部刺激的響應(yīng)方面有高度異質(zhì)性。單細(xì)胞分析是在單個(gè)細(xì)胞水平研究成百上千個(gè)細(xì)胞,它可以獲得傳統(tǒng)的基于大量細(xì)胞平均值的研究中無(wú)法得到重要數(shù)據(jù)。因此,該技術(shù)于2007年被《麻省理工大學(xué)技術(shù)綜述》評(píng)為國(guó)際十大突破技術(shù)之一。單細(xì)胞克隆分析可以在單細(xì)胞水平研究細(xì)胞的生長(zhǎng)動(dòng)力學(xué)機(jī)理、分裂或分化機(jī)制。從混合的細(xì)胞群體中分離單個(gè)細(xì)胞是進(jìn)行單細(xì)胞克隆培養(yǎng)的前提。由于微流控芯片具有獨(dú)特的單細(xì)胞操作能力和對(duì)細(xì)胞微環(huán)境精確控制的潛力,現(xiàn)已廣泛應(yīng)用于單細(xì)胞捕獲和分析。但是,單個(gè)細(xì)胞在現(xiàn)有微流控裝置中的成活率和克隆集落形成率非常低。而且,芯片上的細(xì)胞很難相互獨(dú)立的回收出來(lái)以便利用傳統(tǒng)設(shè)備進(jìn)行后續(xù)分析。因此將大量單細(xì)胞接種到獨(dú)立的培養(yǎng)室,是可以解決單細(xì)胞克隆擴(kuò)增研究的關(guān)鍵問(wèn)題之一。本文設(shè)計(jì)并制作了一款可與標(biāo)準(zhǔn)孔板兼容的微流控芯片。該芯片利用集成可調(diào)節(jié)閥門(mén)和相應(yīng)通孔篩選并回收符合尺寸要求的單個(gè)微球到標(biāo)準(zhǔn)384孔板上,確保實(shí)現(xiàn)每孔一個(gè)微球。該芯片具有三個(gè)獨(dú)立層（氣體層、薄膜層和流體層）和兩種操作模式（高通量捕獲單細(xì)胞/微球或基于細(xì)胞/微球大小的動(dòng)態(tài)篩選和可尋址回收）。首先,本文采用理論計(jì)算、數(shù)值模擬... 

【文章頁(yè)數(shù)】：65 頁(yè)

【學(xué)位級(jí)別】：碩士

【文章目錄】：
摘要
Abstract
Acknowledgement
Nomenclature
Chapter 1 Introduction
    1.1 Background and significance
        1.1.1 Background
        1.1.2 Significance
    1.2 Current situation and analysis of research
        1.2.1 Current situation of research
        1.2.2 Literature review
    1.3 Objective
    1.4 Key novelty
    1.5 Thesis outline
Chapter 2 Design and working principle
    2.1 Microfluidics platform design
        2.1.1 Platform design
        2.1.2 Chip design
    2.2 Working principle
    2.3 Working modes
    2.4 Summary
Chapter 3 Analytical and numerical methods
    3.1 Solid mechanics simulation
        3.1.1 Governing equations
        3.1.2 Model Geometry
        3.1.3 Boundary condition
        3.1.4 Model validation
    3.2 Fluid mechanics simulation
        3.2.1 Governing equations
        3.2.2 Model Geometry
        3.2.3 Boundary conditions
        3.2.4 Model validation
    3.3 Summary
Chapter 4 Experimental methods
    4.1 Chip manufacture
    4.2 Membrane deformation study
    4.3 Fluid flow study
    4.4 Microsphere trapping and release
    4.5 Summary
Chapter 5 Results and discussion
    5.1 The hydrodynamic models
        5.1.1 PDMS membrane deformation study
        5.1.2 Flow resistance study
        5.1.3 Flow rate study
    5.2 Shear stress study
    5.3 Chip manufacture parameters study
        5.3.1 Membrane manufacture study
        5.3.2 Alignment study
    5.4 Single microspheres screening results
    5.5 Summary
Conclusions
References
Author’s Publications and other outcomes
詳細(xì)中文摘要



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