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Generation of tumor spheroids using a droplet-based microfluidic device for photothermal therapy
Microsystems & Nanoengineering ( IF 7.3 ) Pub Date : 2020-06-29 , DOI: 10.1038/s41378-020-0167-x
Jong Min Lee 1, 2 , Ji Wook Choi 1 , Christian D Ahrberg 1 , Hyung Woo Choi 3 , Jang Ho Ha 1 , Seok Gyu Mun 4 , Sung Joon Mo 4 , Bong Geun Chung 1
Affiliation  

Despite their simplicity, monolayer cell cultures are not able to accurately predict drug behavior in vivo due to their inability to accurately mimic cell-cell and cell-matrix interactions. In contrast, cell spheroids are able to reproduce these interactions and thus would be a viable tool for testing drug behavior. However, the generation of homogenous and reproducible cell spheroids on a large scale is a labor intensive and slow process compared to monolayer cell cultures. Here, we present a droplet-based microfluidic device for the automated, large-scale generation of homogenous cell spheroids in a uniform manner. Using the microfluidic system, the size of the spheroids can be tuned to between 100 and 130 μm with generation frequencies of 70 Hz. We demonstrated the photothermal therapy (PTT) application of brain tumor spheroids generated by the microfluidic device using a reduced graphene oxide-branched polyethyleneimine-polyethylene glycol (rGO-BPEI-PEG) nanocomposite as the PTT agent. Furthermore, we generated uniformly sized neural stem cell (NSC)-derived neurospheres in the droplet-based microfluidic device. We also confirmed that the neurites were regulated by neurotoxins. Therefore, this droplet-based microfluidic device could be a powerful tool for photothermal therapy and drug screening applications.



中文翻译:

使用基于液滴的微流体装置用于光热治疗的肿瘤球体的生成

尽管它们很简单,但单层细胞培养无法准确预测体内药物行为,因为它们无法准确模拟细胞-细胞和细胞-基质相互作用。相比之下,细胞球体能够重现这些相互作用,因此将成为测试药物行为的可行工具。然而,与单层细胞培养相比,大规模生成同质和可重复的细胞球体是一个劳动密集型和缓慢的过程。在这里,我们提出了一种基于液滴的微流体装置,用于以统一的方式自动、大规模地生成同质细胞球体。使用微流体系统,球体的大小可以调整到 100 到 130 μm 之间,生成频率为 70 Hz。我们展示了使用还原氧化石墨烯支化聚乙烯亚胺聚乙二醇 (rGO-BPEI-PEG) 纳米复合材料作为 PTT 剂的微流体装置产生的脑肿瘤球体的光热疗法 (PTT) 应用。此外,我们在基于液滴的微流体装置中生成了大小均匀的神经干细胞 (NSC) 衍生神经球。我们还证实神经突受神经毒素调节。因此,这种基于液滴的微流体装置可以成为光热疗法和药物筛选应用的有力工具。我们还证实神经突受神经毒素调节。因此,这种基于液滴的微流体装置可以成为光热疗法和药物筛选应用的有力工具。我们还证实神经突受神经毒素调节。因此,这种基于液滴的微流体装置可以成为光热疗法和药物筛选应用的有力工具。

更新日期:2020-06-29
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