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Ultrathin Polymer Membranes with Patterned Micrometric Pores for Organs-on-chips

机译：超薄聚合物膜带图案化微米孔用于芯片上的器官

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The basal lamina or basement membrane (BM) is a key physiological system that participates in physicochemical signaling between tissue types. Its formation and function are essential in tissue maintenance, growth, angiogenesis, disease progression, and immunology. In vitro models of the BM, e.g., Boyden and transwell chambers, are common in cell biology and lab-on-a-chip devices where cells require apical and basolateral polarization. Extravasation, intravasation, membrane transport of chemokines, cytokines, chemotaxis of cells, and other key functions are routinely studied in these models. The goal of the present study was to integrate a semipermeable ultrathin polymer membrane with precisely positioned pores of 2 μm diameter in a microfluidic device with apical and basolateral chambers. We selected poly (L-lactic acid) (PLLA), a transparent biocompatible polymer, to prepare the semipermeable ultrathin membranes. The pores were generated by pattern transfer using a three-step method coupling femtosecond laser machining, polymer replication, and spin coating. Each step of the fabrication process was characterized by scanning electron microscopy to investigate reliability of the process and fidelity of pattern transfer.In order to evaluate the compatibility of the fabrication method with organs-on-a-chip technology, porous PLLA membranes were embedded in polydimethylsiloxane (PDMS) microfluidic devices and used to grow human umbilical vein endothelial cells (HUVECS) on top of the membrane with perfusion through the basolateral chamber. Viability of cells, optical transparency of membranes and strong adhesion of PLLA to PDMS were observed, thus confirming the suitability of the prepared membranes for use in organs-on-a-chip devices.
机译：基底层或基底膜（BM）是关键的生理系统，参与组织类型之间的物理化学信号传递。它的形成和功能对组织维持，生长，血管生成，疾病进展和免疫学至关重要。 BM的体外模型，例如Boyden和Transwell室，在细胞需要顶极和基底外侧极化的细胞生物学和芯片实验室设备中很常见。在这些模型中常规研究了外渗，内渗，趋化因子的膜运输，细胞因子，细胞趋化性和其他关键功能。本研究的目的是在带有顶腔和基底外侧腔的微流控设备中集成具有2μm直径精确定位孔的半透性超薄聚合物膜。我们选择了一种透明的生物相容性聚合物聚（L-乳酸）（PLLA）来制备半透性超薄膜。使用飞秒激光加工，聚合物复制和旋涂的三步法，通过图案转移产生孔。通过扫描电子显微镜对制造过程的每个步骤进行表征，以研究该过程的可靠性和图案转印的保真度。为了评估该制造方法与器官上芯片技术的兼容性，将多孔PLLA膜嵌入其中。聚二甲基硅氧烷（PDMS）微流控设备，用于通过基底外侧腔灌注在膜顶部生长人脐静脉内皮细胞（HUVECS）。观察到细胞的活力，膜的光学透明性和PLLA对PDMS的强粘附性，从而证实了制备的膜适用于片上器官装置中的适用性。

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