Department of Nanobiomedical Science, Dankook University, Cheonan 330-714, Republic of Korea.
College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
Biomol Ther (Seoul). 2014 Jul;22(4):355-62. doi: 10.4062/biomolther.2014.078.
We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.
我们开发了一种基于微流控细胞培养阵列的全自动高通量药物筛选(HTDS)系统,以进行组合化疗。该系统有 64 个可单独寻址的细胞培养室,通过两个微流控扩散混合器可以生成两种不同药物的顺序组合浓度。每个扩散混合器有两个集成的微泵,分别连接到介质和药物储存器,以生成所需的组合,而无需任何额外的设备(如注射器泵)来灌注溶液。细胞阵列在几天内通过编程的 LabVIEW 系统周期性地暴露于药物组合中,在将细胞接种到微流控设备后无需额外处理,并且与以前的系统相比,该设备不需要连续生成溶液。因此,每个储液器中每次实验消耗的药物总量少于几百微升。通过用姜黄素和肿瘤坏死因子相关凋亡诱导配体(TRAIL)的组合处理来研究前列腺癌 PC3 细胞系的活力,证明了该系统的实用性。我们的结果表明,该系统可用于筛选和优化组合化疗中抗癌药物的组合,所需试剂用量很少。