中文摘要：

开发了一种多层纸芯片细胞培养平台,将乳腺癌细胞分别接种于多层的图形化纸芯片的亲水区,折叠后构建了仿真实体肿瘤。多层纸芯片覆以微孔薄膜,用以仿真血管内皮层。培养不同时间后,拆解多层纸芯片检测乳腺癌组织内各层面的细胞形态、存活率、细胞周期分布以及细胞内乳酸含量。实验结果显示,各层纸芯片培养的乳腺癌细胞存活率均高于80%,并形成了类组织结构。芯片乳腺癌组织内部呈酸化倾向,且酸化程度随着培养时间的延长而升高。与二维（2D）培养细胞相比较,纸芯片乳腺癌组织内细胞增殖比例显著降低（15%vs 60%）。多层纸芯片乳腺癌组织显示了更接近体内情况的药物反应机制,细胞存活率随阿霉素浓度升高呈现缓慢下降趋势,IC50值显著高于2D培养细胞组（5.0μmol/L vs 1.144μmol/L）。这种多层纸芯片乳腺癌组织微阵列构建简便、仿真度高,有望成为抗肿瘤药物反应测试的有力工具。

英文摘要：

This paper describes a multi-layer paper-supported breast cancer tissue array. The paper-based microchip with arrayed hydrophilic spots was fabricated by wax printing. After cell seeding,the microchip was folded to form an artificial solid tumor,and the multilayer paper was covered by a layer of microporous membrane that mimics endothelial layer. After culturing the paper-supported breast cancer tissue for a certain period of time,the multi-layer device was unfold thus enabling detections of cell survival,proliferation,morphology and metabolism on different layers. Breast cancer cells cultured on paper had a survival rate 80% and aggregated into tumor spheroids. Intracellular lactic acid levels increased with the extension of culture time. Compared to two dimensional（ 2D） counterparts,the decreased fraction of S phase cell（ 15%vs 60%） was detected. The paper-supported breast cancer tissue showed a drug response mechanism similar to the tumor in vivo. Cancer cells within the tissue were less sensitive to doxorubicin and the IC50 value detected was significantly higher than that obtained with 2D cultures（ 5 μmol / L vs 1. 14 μmol / L）. The multi-layer paper-supported breast cancer tissue array developed in this work featured simple tissue reconstruction and easy operation,thus providing an ideal tool for anti-cancer drug testing.