Integrating biological vasculature into a multi-organ-chip microsystem
Integrating biological vasculature into a multi-organ-chip microsystem
复制标题
DOI：
10.1039/c3lc50217a
复制
发表时间：
2013-01-01
期刊：
影响因子：
6.1
通讯作者：
Horland, Reyk
中科院分区：
文献类型：
--
作者：
Schimek, Katharina;Busek, Mathias;Horland, Reyk
一个基于芯片的系统模仿人体心血管系统的运输功能已经建立在分钟，但标准化的微系统规模。蠕动的芯片上微泵在微通道回路内产生在广泛可调节的生理范围内的脉动剪切应力，所述微通道回路完全覆盖在与人真皮微血管内皮细胞的所有流体接触表面上。这种微血管运输系统可以在4天内重复建立，独立于单个内皮细胞供体背景。它通过500 mm宽的微流体通道将两个标准的组织培养隔室相互连接，每个隔室的直径为5 mm。通过应用于插入物的双光子激光消融技术实现了进一步的血管分支和血管直径减小至约40 mm宽度的微血管尺度，该技术旨在方便地在稍后的时间在组织培养隔室中建立单独的器官等同物。芯片布局确保了生理液体与组织的比例。此外，深入的显微镜分析揭示了微调调整的内皮细胞行为的局部剪切应力沿着微血管系统。时间推移和3D成像双光子显微镜被用来可视化的细节的时空粘附的内皮细胞的通道系统和彼此。第一个指示性的长期实验显示，在两周和四周内性能稳定。该系统的潜在应用，为未来建立人的芯片系统和基础的人类内皮细胞的研究进行了讨论。
A chip-based system mimicking the transport function of the human cardiovascular system has been established at minute but standardized microsystem scale. A peristaltic on-chip micropump generates pulsatile shear stress in a widely adjustable physiological range within a microchannel circuit entirely covered on all fluid contact surfaces with human dermal microvascular endothelial cells. This microvascular transport system can be reproducibly established within four days, independently of the individual endothelial cell donor background. It interconnects two standard tissue culture compartments, each of 5 mm diameter, through microfluidic channels of 500 mm width. Further vessel branching and vessel diameter reduction down to a microvessel scale of approximately 40 mm width was realised by a two-photon laser ablation technique applied to inserts, designed for the convenient establishment of individual organ equivalents in the tissue culture compartments at a later time. The chip layout ensures physiological fluid-to-tissue ratios. Moreover, an in-depth microscopic analysis revealed the fine-tuned adjustment of endothelial cell behaviour to local shear stresses along the microvasculature of the system. Time-lapse and 3D imaging two-photon microscopy were used to visualise details of spatiotemporal adherence of the endothelial cells to the channel system and to each other. The first indicative long-term experiments revealed stable performance over two and four weeks. The potential application of this system for the future establishment of human-on-a-chip systems and basic human endothelial cell research is discussed.