微器官三维组装芯片的基础研究

The organ-on-chip is a device that simulates the physiological functions of human organs on a chip-sized biomaterial. As a novel strategy for drug tests, its development is remarkable in recent years. For better simulation of drug metabolism in human body, the applicant propose to combine The organ-on-chip is a device that simulates the physiological functions of human organs on a chip-sized biomaterial. As a novel strategy for drug tests, its development is remarkable in recent years. For better simulation of drug metabolism in human body, it is necessary to combine the coupled-organ-on-chips (body-on-chips) and physiologically based pharmacokinetics. This process requires precise control of masses of micro-organs in different chips and the flux of broth, and construction of different broth circulations in sub-chips. Based on these considerations, the applicant will try to construct a three-dimensional, layered and integrated (liver and heart coupled) organ-on-chip. The hydrogel embedding and 3D printing techniques will be used to construct relative isolated microfluidic system, for the independent control of micro-organ in different layers. Furthermore, with the high-throughput, quantitated and progressive analysis from micro-organ to cell markers, the interaction between heart and liver during drug assessment can be resolved. This study will construct a pharmacokinetics approved coupled-organ-on chips in heart and liver related medicine selection. It will also inspire the new designs of coupled-organ-on-chips to mimic the microenvironment in vivo.

器官芯片是在芯片大小的生物材料上模拟人体器官的生理功能，作为药物筛选的新手段近年来获得迅猛的发展。为更好地模拟人体中的药物代谢过程，需将多器官偶联芯片（人体芯片）和生理药代动力学模型结合，这要求更精确地控制不同器官芯片中的微器官质量、培养液流速以及在子芯片中建立不同的培养液循环。由此为出发点，申请者以肝脏微器官偶联心脏微器官为例，尝试建立层状结构的三维一体化芯片；利用水凝胶包埋技术及3D打印技术分层构造相对独立的的微流控系统以实现对不同微器官层的分别控制；进一步运用高通量定量分析技术，从微器官到细胞标记物层层递进的策略解析药物评价过程中心脏和肝脏之间的相互作用和影响。该研究将在心脏-肝脏相关药物筛选研究中建立符合生理药代动力学模型的一体化芯片，同时为体内微环境模拟的多器官芯片偶联方式提供新思路。

器官芯片是在芯片大小的生物材料上模拟人体器官的生理功能，作为药物筛选的新手段近年来获得迅猛的发展。为更好地模拟人体中的药物代谢过程，需将多器官偶联芯片（人体芯片）和生理药代动力学模型结合，这要求更精确地控制不同器官芯片中的微器官质量、培养液流速以及在子芯片中建立不同的培养液循环。由此为出发点，本项目以双器官偶联微芯片为例，尝试建立层状结构的三维一体化芯片；利用新型芯片设计及Gel-MA（甲基丙烯酸酯化明胶）水凝胶包埋技术分层构造相对独立的的微流控系统以实现对不同微器官层的分别控制；进一步运用高通量定量分析技术，从天然药物有效成分到细胞标记物层层递进的代谢组学策略解析药物。该研究将在基于双器官微芯片的药物筛选研究中建立符合生理药代动力学模型的一体化芯片，从代谢组学层次阐明了生物活性物质的组成差异，同时为体内微环境模拟的多器官芯片偶联方式提供新思路。