上海大学学报(自然科学版) ›› 2025, Vol. 31 ›› Issue (2): 212-222.doi: 10.12066/j.issn.1007-2861.2578

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面向微血管组织构建的多层微流控芯片

岳 涛, 姜 宁, 王 越, 杨卉颖, 刘 娜, 徐祎春   

  1. 1. 上海大学 机电工程与自动化学院, 上海 200444; 2. 上海大学 未来技术学院, 上海 200444; 3. 上海生物芯片有限公司/生物芯片上海国家工程研究中心, 上海 201203
  • 收稿日期:2024-03-19 出版日期:2025-04-30 发布日期:2025-04-30
  • 通讯作者: 岳 涛 E-mail:tao yue@shu.edu.cn
  • 基金资助:
    国家自然科学基金资助项目 (62373235, 62303290, 62073208); 上海市自然基金面上资助项目(23ZR1423700)

A multilayer microfluidic chip for microvascular tissue construction

YUE Tao, JIANG Ning, WANG Yue, YANG Huiying,LIU Na, XU Yichun   

  1. 1. School of Mechatronic Engineering and Automation, Shanghai University, Shanghai 200444, China; 2.School of Future Technology, Shanghai University, Shanghai 200444, China; 3. Shanghai Biochip Corporation (SBC)/National Engineering Research Center for Biochip at Shanghai, Shanghai 201203, China
  • Received:2024-03-19 Online:2025-04-30 Published:2025-04-30

摘要: 微流控技术为体外构建人造微血管组织提供了一种有效方法. 提出一种三层微流控芯片, 利用聚碳酸酯 (polycarbonate, PC) 多孔膜, 将培养液通道与组织腔室分隔开. PC 多孔膜的微孔结构可以在垂直方向上形成毛细管爆破阀, 使得水凝胶可以在液体表面张力作用下充满组织腔室, 并且不会泄露到培养液通道中, 从而确保三维流体微环境的有效构建. 建立COMSOL 有限元模型, 对单矩形腔室的三维流体微环境进行仿真, 证明所提出的三层微流控芯片可以提供刺激血管形成的流速环境. 利用所提出的三层微流控芯片测试了内皮祖细胞和人脐带静脉内皮细胞的血管分化能力, 并在多组织腔室阵列芯片上构建了培养至第 8 天左右的多种形状微血管网络. 所提出的三层微流控芯片具有设计灵活的特点, 可以改变组织腔室的形状, 以高通量提供不同的流体条件, 将为研究流体因素对微血管生长的影响提供一种潜在的工程化手段.

关键词: 多层, 微流控芯片, 多孔膜, 三维流体微环境, 微血管网络

Abstract: Microfluidic technology is effective for constructing artificial microvascular tissues in vitro. A three-layer microfluidic chip was reported to use a polycarbonate (PC) porous membrane to separate culture fluid channels from tissue chambers. The micro-porous structure of the PC porous membrane formed a capillary bursting valve in the vertical direction to allow the hydrogel to fill the tissue chambers under the surface tension of the fluid and keep it from leaking into the culture fluid channels to ensure that the three-dimensional fluid microenvironment was effectively constructed. A COMSOL finite element model was established to simulate the three-dimensional fluidic microenvironment of a sin-gle rectangular chamber, and it was used to demonstrate that the three-layer microfluidic chip could provide a flow environment to stimulate blood vessel formation. The vascular differentiation abilities of endothelial progenitor cells and human umbilical vein endothelial cells were tested using the proposed three-layer microfluidic chip, and multiple shapes of microvessel networks cultured for up to approximately eight days were constructed on top of the multi-tissue chamber array chip. This three-layer microfluidic chip had the design flexibility to change the shape of the tissue chambers to provide different fluidic conditions at high throughput and provided a potential engineering tool to study the effects of fluidic factors on microvascular growth.

Key words: multilayer, micro?uidic chip, porous membrane, three-dimensional ?uidic microenvironment, microvascular network

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