肿瘤微血管芯片的制备及其应用  

A tumor capillary model preparation based on microfluidic chip for permeability assay

作　　者：翟万银[1,2,3] 吴蕾[1] 贾春平[1] 邵建波[1] 徐元森[1] 

机构地区：[1]中国科学院上海微系统与信息技术研究所传感技术联合国家重点实验室,上海200068 [2]中国科学院研究生院,北京100049 [3]中国科学院上海硅酸盐研究所,上海200050

出　　处：《功能材料与器件学报》2011年第5期505-512,共8页Journal of Functional Materials and Devices

摘　　要：肿瘤血管结构不同于正常组织血管,由内皮细胞松散地围成不完整的管道,呈高通透性。为建立体外简便、有效、低廉的肿瘤血管模型,本研究采用微加工技术,制作了肿瘤血管微流控芯片。芯片包括24 mm长50μm宽40μm深的微管道和一侧的微腔体以及两者之间的微缝。微管道中部设有膨胀区域以模拟肿瘤血管结构。在微管道内导入血管内皮细胞,培养形成细胞壁垒。通过促进细胞迁移而使得细胞壁垒出现稳定的泄漏点,使血管芯片具有通透性,并对体内调控血管通透性分子组胺和MMP2产生与体内相似的反应。在此基础上发现,原花青素对血管通透性有显著抑制作用,而抗癌药物依立替康则有促进作用,显示该肿瘤血管微流控芯片初步具备了肿瘤血管通透性调控分析的功能。Tumor capillary blood vessel is much different from vessel in normal tissues. Based on microfluidic chip of normal tissue vessels which was prepared in this laberatory, a novel tumor capillary model preparation has been made using microfabrication technology. The model consists of （1） a microchannel with 24 mm in length,50 ixm in width and 40 p,m in depth, （2） a microehamber linked to a microchannel by micro gaps. The microehannel was expanded at three sites in the middle part to mimic the irregular structure of tumor capillary. After the microchannel being transfused with human umbilical vein endothelial cells, the chip was cultured for 10 d to obtain an integrated cell barrier. Permeability has been achieved after 24 h induction for cell migration by adjusting the height of culture medium in pipette tip of inlet and outlet. The permeability of microfluidic chip well mimicked the characteristics of tumor blood vessels. The chip can respond just like in vivo to histamine and metalloprotease -2 which can induce high permeability. In present study, this microfluidic chip has been used to measure the effect of procyanidins and irinotecan, a clinical medicine for curing cancers, on permeability. The result showed that procyanidins at 0.1, 1 and 2μg/mL can inhibit the permeability. All these data proved the prepared microfluidic chip has the primary function for permeability assay.

关 键 词：肿瘤血管 微流控芯片 血管内皮细胞 通透性 

分 类 号：TB[一般工业技术]