用于细胞三维培养的集成微柱阵列的微流控芯片设计与验证

摘要

设计并验证了一种用于细胞三维培养的集成微柱阵列的微流控芯片.芯片由一片聚二甲基硅氧烷(PDMS)沟道片和一片玻璃盖片组成, 在PDMS沟道片上集成了一个由两排微柱阵列围成的细胞培养室和两条用于输送培养基的侧沟道.微柱间距直接影响了芯片的使用性能, 是整个芯片设计的关键.基于数值模拟和实验验证, 本研究对微柱间距进行了优化设计.优化后的微流控芯片可以很好地实现细胞与细胞外基质模拟材料混合液的稳定注入、培养基中营养物质向培养室内的快速扩散和细胞代谢物的及时排出.在芯片上进行了神经干细胞的三维培养, 证明了芯片上构建的细胞体外微环境的稳定性.%A microfluidic chip with micropillar arrays for three-dimensional (3D) cell culture was designed and validated.The chip consisted of a polydimethylsiloxane (PDMS) channel plate and a glass cover plate.One cell culture chamber composed of two rows of micropillar arrays and two lateral channels for transporting the culture medium were integrated on the PDMS channel plate.The spacing between micropillars directly affects the chip performance, which is critical for the design of the chip.In this work, the spacing between micropillars was optimized by numerical simulation and experimental validation.With the optimized microfluidic chip, the mixture of cells and extracellular matrix mimics could be steadily injected into the cell culture chamber, the nutrients in the culture medium from the lateral channels could quickly diffuse into the chamber, and the cell metabolites could also timely diffuse out of the chamber.To test the stability of the microenvironment in the microfluidic chip, neural stem cells were three-dimensionally cultured.