A Microfluidic Device Platform Reconstructing Lung Pattern for Cancer Immunotherapy Applications

Yu-Chen Chen, Han-Jung Liao, Jean-An Chich, Pin-Tzu Lai, Yi-Ying Liang, Kang-Yun Lee, Wei-Lun Sun, S. Ho, Yu-Shiuan Wang, Wan-Chen Huang, Wei-Chiao Chang, Sung-Yang Wei, Cheng-Hsien Liu
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Abstract

Cancer is one of the leading causes of death globally. To simulate a similar environment of human tissue is the difficulty in cancer research. The development of 3D culture model is used to imitate the environment to provide a potential research strategy. Matrigel is the most commonly used material for 3D culture models. However, it is derived from murine tumors, unsuitable for clinical applications. In this study, the methacrylated gelatin (GelMA) was blended with type I collagen as a biomaterial in our microfluidic device. We further optimized the device design; it can perform entirely experimental functions without requiring complicated parts such as pumps and valves. On this microfluidic platform, the biocompatible hydrogel and cells could be patterned via liquid dielectrophoresis (LDEP) and dielectrophoretic force (DEP). The experimental results demonstrated that the human lung cancer cells were patterned via both DEP/LDEP and light-curing hydrogel with low cell mortality. The patterned cells' mortality rate is less than 5% after 24 hr of cultivation. Our results suggest the potential of this device for future clinical cancer study applications. Furthermore, we also expect to achieve bionic tumors and explore the interaction between 3D cell models and drugs.
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一种用于肿瘤免疫治疗的肺形态重建微流控装置平台
癌症是全球死亡的主要原因之一。模拟类似的人体组织环境是癌症研究的难点。利用三维培养模型的发展来模拟环境,为研究提供潜在的策略。矩阵是3D培养模型最常用的材料。然而,它来源于小鼠肿瘤,不适合临床应用。在本研究中,甲基丙烯酸明胶(GelMA)与I型胶原蛋白混合作为微流控装置中的生物材料。我们进一步优化了器件设计;它可以完全执行实验功能,而不需要复杂的部件,如泵和阀门。在该微流控平台上,生物相容性水凝胶和细胞可以通过液体介电泳(LDEP)和介电泳力(DEP)进行图图化。实验结果表明,DEP/LDEP和光固化水凝胶均可制备人肺癌细胞,且细胞死亡率低。培养24小时后,花纹细胞死亡率低于5%。我们的研究结果表明该装置在未来临床癌症研究中的应用潜力。此外,我们还期望实现仿生肿瘤,并探索三维细胞模型与药物的相互作用。
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