Korea Institute of Machinery and Materials, Daegu Research Center for Medical Devices and Rehab. Engineering, Department of Medical Device, 330 Techno Sunhwan-ro, Yuga-myeon, Dalsung-gun, Daegu 42994, Republic of Korea.
Korea Institute of Machinery and Materials, Daegu Research Center for Medical Devices and Rehab. Engineering, Department of Medical Device, 330 Techno Sunhwan-ro, Yuga-myeon, Dalsung-gun, Daegu 42994, Republic of Korea; Yeungnam University, School of Mechanical Engineering, 280 Daehak-ro, Gyeongsan-si, Gyeongsanbuk-do 38541, Republic of Korea.
J Control Release. 2018 Apr 10;275:201-207. doi: 10.1016/j.jconrel.2018.02.029. Epub 2018 Feb 21.
In vivo tumors develop in a three-dimensional manner and have unique and complex characteristics. Physico-biochemical barriers on tumors cause drug resistance and limit drug delivery efficiency. Currently, 2D cancer cell monolayer platforms are frequently used to test the efficiency of new drug materials. However, the monolayer platform generally overestimates drug efficiency because of the absence of physico-biochemical barriers. Many literatures indicated that a 3D tumor spheroid model has very similar characteristics to in vivo tumor models, and studies demonstrated the accurate prediction of drug efficiency using this model. The use of a 3D tumor spheroid model in drug development process remains challenging because of the low generation yield and difficulties in size control. In this study, we developed a droplet-based microfluidic system that can generate cancer cells encapsulated by micro-droplets with very high generation yield (16-20 Hz, 1000 droplets/min). The system can control the number of encapsulated cancer cells in the droplet or diameter of the 3D spheroid model precisely between 50 and 150 μm. Moreover, the formed 3D tumor spheroid model can be cultured for >2 weeks by an additional step of droplet disruption and recollection, and can grow up to 245 μm in diameter.
在体内，肿瘤以三维方式生长，具有独特而复杂的特性。肿瘤的物理-生化屏障导致药物耐药性，并限制了药物输送效率。目前，二维癌细胞单层平台常用于测试新药材料的效率。然而，由于缺乏物理-生化屏障，单层平台通常会高估药物效率。许多文献表明，三维肿瘤球体模型与体内肿瘤模型具有非常相似的特征，并且研究表明使用该模型可以准确预测药物效率。由于生成产量低和尺寸控制困难，3D 肿瘤球体模型在药物开发过程中的应用仍然具有挑战性。在本研究中，我们开发了一种基于液滴的微流控系统，该系统可以以非常高的生成产量（16-20 Hz，1000 个液滴/分钟）生成微液滴包封的癌细胞。该系统可以精确控制液滴中包封的癌细胞数量或 3D 球体模型的直径在 50-150 μm 之间。此外，通过额外的液滴破坏和收集步骤，形成的 3D 肿瘤球体模型可以培养超过 2 周，并且可以生长到 245 μm 的直径。
