Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening,Lab on a Chip

当前位置： X-MOL 学术 › Lab Chip › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Cardiac microphysiological devices with flexible thin-film sensors for higher-throughput drug screening
Lab on a Chip ( IF 6.1 ) Pub Date : 2017-09-28 00:00:00 , DOI: 10.1039/c7lc00740j
Johan U. Lind _{1,

2,

3,

4,

5} , Moran Yadid _{1,

2,

3,

4,

5} , Ian Perkins _{1,

2,

3,

4,

5} , Blakely B. O'Connor _{1,

2,

3,

4,

5} , Feyisayo Eweje _{1,

2,

3,

4,

5} , Christophe O. Chantre _{1,

2,

3,

4,

5} , Matthew A. Hemphill _{1,

2,

3,

4,

5} , Hongyan Yuan _{1,

2,

3,

4,

5} , Patrick H. Campbell _{1,

2,

3,

4,

5} , Joost J. Vlassak _{2,

4,

5,

6} , Kevin K. Parker _{1,

2,

3,

4,

5}

Affiliation

Microphysiological systems and organs-on-chips promise to accelerate biomedical and pharmaceutical research by providing accurate in vitro replicas of human tissue. Aside from addressing the physiological accuracy of the model tissues, there is a pressing need for improving the throughput of these platforms. To do so, scalable data acquisition strategies must be introduced. To this end, we here present an instrumented 24-well plate platform for higher-throughput studies of engineered human stem cell-derived cardiac muscle tissues that recapitulate the laminar structure of the native ventricle. In each well of the platform, an embedded flexible strain gauge provides continuous and non-invasive readout of the contractile stress and beat rate of an engineered cardiac tissue. The sensors are based on micro-cracked titanium–gold thin films, which ensure that the sensors are highly compliant and robust. We demonstrate the value of the platform for toxicology and drug-testing purposes by performing 12 complete dose–response studies of cardiac and cardiotoxic drugs. Additionally, we showcase the ability to couple the cardiac tissues with endothelial barriers. In these studies, which mimic the passage of drugs through the blood vessels to the musculature of the heart, we regulate the temporal onset of cardiac drug responses by modulating endothelial barrier permeability in vitro.

中文翻译：

带有柔性薄膜传感器的心脏微生理设备，用于高通量药物筛选

微生理系统和片上器官有望通过提供准确的体外实验来加速生物医学和药物研究人体组织的复制品。除了解决模型组织的生理准确性外，迫切需要改善这些平台的通量。为此，必须引入可伸缩的数据采集策略。为此，我们在这里提出了一种仪器化的24孔板平台，用于工程化的人类干细胞衍生的心肌组织的高通量研究，该组织概括了天然心室的层状结构。在平台的每个孔中，嵌入式挠性应变仪可连续无创地读出工程心脏组织的收缩应力和搏动率。传感器基于微裂纹的钛金薄膜，可确保传感器具有高度的适应性和耐用性。通过对心脏和心脏毒性药物进行12项完整的剂量反应研究，我们证明了该平台对毒理学和药物测试目的的价值。此外，我们展示了将心脏组织与内皮屏障结合在一起的能力。在这些模拟药物通过血管到达心脏肌肉组织的研究中，我们通过调节内皮屏障通透性来调节心脏药物反应的时间发作体外。

更新日期：2017-10-26

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11