基于微流控芯片的线粒体外膜透化信息提取和模型研究

项目名称： 基于微流控芯片的线粒体外膜透化信息提取和模型研究

项目编号： No.81201165

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 钱翔

作者单位： 清华大学

项目金额： 23万元

中文摘要： 我们采用微流控芯片产生姜黄素等药物的浓度梯度，促使在其中长时间培养的人乳腺癌细胞MCF-7凋亡，通过观察细胞凋亡过程中线粒体外面透化（MOMP）的现象，在细胞群体统计分析的意义上建立起了一套基于微流控芯片的药物筛选平台。通过进一步的文献调研和分析发现，生物学研究者在研究细胞凋亡机制的过程中，实验所获的信号通路变的越来越复杂，而我们现有的平台仅仅包含了MOMP"有/无"发生的逻辑二值化信息。因而，本申请着眼于利用微流控芯片精确的药物激励和连续的灌流培养特性，通过实验获取MOMP相关的细胞凋亡过程中线粒体膜间几种重要分子在细胞内分布的时间和空间信息，从而建立MOMP在细胞内部的动态模型，力图揭示MOMP产生过程中的"延时效应"、"开/关效应"是否和药物的激励浓度和种类有着对应的关系。这一研究可以为抗癌药物的作用提供一定的量化衡量指标，建立更加精确"效能"信息，具有一定的科学意义和应用前景。

中文关键词： 微流控芯片；三维流体聚焦；荧光图像处理；线粒体外膜透化；

英文摘要： We employed the microfluidic chip to produce the concentration gradient of the curcumin to stimulate the MCF-7 cells to apoptosis.By observing the mitochondrial outer membrane permeabilization(MOMP) during the apoptosis process of the cells, a mcirofluidic chip based drug screening system by means of statical analysis of cells population was successfully constructed.According to the recent literature, more and more complicated signaling pathways were acquired during the research of the apoptosis mechanism of cell. Our system, however, only incorporated the "On/Off" logical status of MOMP occurrence to screening the effectiveness of certain drug. Thus, the current proposal aims to incorporate the outstanding feature of the microfluidic chips which can accurate delivery of drugs, both spatially and temporally, to aqcuire the information of cellular distribution of several important molecules located in the intermembrane space of the mitochondria during MOMP related cell apoptosis and to modeling the MOMP process in the cell. The "delay effect" and "switch effect" of the MOMP and whether they are related to the concentration of the drug are proposed to be illustrated. The proposed research are promising to provide accurate and quantitative criteria for anti-cancer drugs, which has significance in scientific researc

英文关键词： microfluidic chip；3-D flow focusing；fluorescence image processing；mitochondrial outer membrane permeabilization；