Abstract：
A modular and 3D compartmentalized microfluidic system with electrospun porous membranes (PMs) for epithelialized organ-on-a-chip systems is presented. Our novel approach involves direct deposition of polymer nanofibers onto a patterned poly(methyl methacrylate) (PMMA) substrate using electrospinning, resulting in an integrated PM within the microfluidic chip. The in situ deposition of the PM eliminates the need for additional assembly processes. To demonstrate the high throughput membrane integration capability of our approach, we successfully deposited nanofibers onto various chip designs with complex microfluidic planar structures and expanded dimensions. We characterized and tested the fully PMMA chip by growing an epithelial monolayer using the Caco-2 cell line to study drug permeability. A comprehensive analysis of the bulk and surface properties of the membrane\'s fibers made of PMMA and polystyrene (PS) was conducted to determine the polymer with the best performance for cell culture and drug transport applications. The PMMA-based membrane, with a PMMA/PVP ratio of 5:1, allowed for the fabrication of a uniform membrane structure along the aligned nanofibers. By modulating the fiber diameter and total thickness of the membrane, we could adjust the membrane\'s porosity for specific cell culture applications. The PMMA-PVP nanofibers exhibited a low polydispersity index value, indicating monodispersed nanofibers and a more homogeneous and uniform fiber network. Both types of membranes demonstrated excellent mechanical integrity under medium perfusion flow rates. However, the PMMA-PVP composition offered a tailored porous structure with modulable porosity based on the fiber diameter and thickness. Our developed platform enables dynamic in vitro modeling of the epithelial barrier and has applications in drug transport and in vitro microphysiological systems.
摘要：
提出了一种具有电纺多孔膜（PM）的模块化和3D分隔微流体系统，用于上皮化的芯片上器官系统。我们的新方法涉及使用静电纺丝将聚合物纳米纤维直接沉积到图案化的聚（甲基丙烯酸甲酯）（PMMA）基材上，导致微流控芯片内的集成PM。PM的原位沉积消除了对额外组装过程的需要。为了证明我们方法的高通量膜集成能力，我们成功地将纳米纤维沉积到具有复杂的微流体平面结构和扩展尺寸的各种芯片设计上。我们通过使用Caco-2细胞系生长上皮单层以研究药物渗透性来表征和测试完全PMMA芯片。对PMMA和聚苯乙烯（PS）制成的膜纤维的体积和表面性能进行了综合分析，以确定具有最佳细胞培养和药物转运应用性能的聚合物。基于PMMA的膜，PMMA/PVP比率为5:1,允许沿着排列的纳米纤维制造均匀的膜结构。通过调节膜的纤维直径和总厚度，我们可以调整膜的孔隙率为特定的细胞培养应用。PMMA-PVP纳米纤维表现出低的多分散指数值,表明单分散的纳米纤维和更均匀和均匀的纤维网络。两种类型的膜在中等灌注流速下都表现出优异的机械完整性。然而,PMMA-PVP组合物基于纤维直径和厚度提供具有可调节孔隙率的定制多孔结构。我们开发的平台可实现上皮屏障的动态体外建模，并可应用于药物运输和体外微生理系统。
