开放式微流控芯片上的肿瘤组织微阵列构建  

Construction of Tumor Tissue Array on An Open-Access Microfluidic Chip

作　　者：林冬果 林锦琼[2] 李佩文 杨娜[2,3] 徐邦牢 刘大渔[1,2,3] LIN Dong-Guo;LIN Jin-Qiong;LI Pei-Wen;YANG Na;XU Bang-Lao;LIU Da-Yu(Laboratory of Clinical Chemistry, The Second Hospital of South China University of Technology, Guangzhou 510180, China;Department of Laboratory Medicine, Guangzhou First People‘s Hospital,Guangzhou Medical University, Guangzhou 510180, China;Clinical Molecular Medicine and Molecular Diagnosis Key Laboratory of Guangdong Province, Guangzhou 510180, China)

机构地区：[1]华南理工大学附属第二医院检验医学研究室,广州510180 [2]广州医科大学附属广州市第一人民医院检验科,广州510180 [3]广东省临床分子医学及分子诊断重点实验室,广州510180

出　　处：《分析化学》2018年第1期113-120,共8页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金(Nos.81371649;81171418;81602434);广州市科创委协同创新项目(Nos.20141A010007;[2016]171)资助~~

摘　　要：构建了一种具有自动形成细胞培养阵列和多步骤灵活操作特点的开放式微流控芯片。此芯片具有3层复合式结构:底层为微通道贯穿的细胞培养池阵列,顶层是开放式培养池,二者之间为一层纳米孔薄膜。纳米孔薄膜具有'透气阻水'的特性,既起到止流阀作用实现液体自动分配,又允许跨膜扩散,模拟血管内皮层扩散屏障结构。结合移液工作站,开放式微流控芯片可以完成细胞换液、药物处理和细胞活力测试等一系列分析步骤。本研究以乳腺癌细胞为模型,在芯片上90 s内可构建包含三维细胞培养和仿真血管内皮的10×10肿瘤组织微阵列。形态学和免疫组织化学检测证实了芯片肿瘤组织的仿真效果。抗肿瘤药物测试结果表明,这种开放式微流控组织阵列芯片允许在仿真条件下进行包含复杂操作步骤的细胞实验,是细胞研究的有利工具。An open-access microfluidic chip which enabled automatic cell distribution and complex multi-step operations was developed.The microfluidic chip featured a key structure in which a nanoporous membrane was sandwiched by a cell culture chamber array layer and a corresponding media reservoir array layer.The microfluidic approach took advantage of the characteristics of the nanoporous membrane.On one side,this membrane permitted the flow of air but not liquid,thus acting as a flow-stop valve to enable automatic cell distribution.On the other side,it allowed diffusion-based media exchange and thus,mimicked the endothelial layer.In synergy with a liquid transferring platform,the open-access microfluidic system enabled complex multi-step operations involving medium exchange,drug treatment,and cell viability testing.By using this microfluidic protocol,a10×10tissue arrays was constructed in90s,followed by schedule-dependent drug testing.Morphological and immunohistochemical assays results indicated that the resultant tumor tissue was faithful to that in vivo.Drug testing assays showed that the microfluidic tissue array promised multi-step cell assays under biomimetic microenvironment,thus providing an advantageous tool for cell research.

关 键 词：开放式微流控芯片 纳米孔薄膜 三维细胞培养 组织微阵列 抗肿瘤药物测试 

分 类 号：R73-3[医药卫生—肿瘤]