Du Guan-Sheng, Pan Jian-Zhang, Zhao Shi-Ping, Zhu Ying, den Toonder Jaap M J, Fang Qun
Department of Chemistry, Institute of Microanalytical Systems, Zhejiang University, Hangzhou, China.
Materials Technology Institute and Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands.
Methods Mol Biol. 2018;1771:203-211. doi: 10.1007/978-1-4939-7792-5_16.
In the last few decades, drug combination therapy has been widely applied in oncology and in other complex diseases. Due to its potential advantage of lower drug toxicity and higher therapeutic efficacy, drug combination treatment has been more and more studied in fundamental labs and pharmacy companies. In this chapter, we report cell-based drug combination screening using a microfluidic droplet system based on a sequential operation droplet array (SODA) technique. In this system, an oil-covered two-dimensional droplet array chip was used as the platform for cell culture and analysis. This chip was fixed in an x-y-z translation stage under control of a computer program. A tapered capillary connected with a syringe pump was coupled with the droplet array chip to achieve multiple droplet manipulations including liquid metering, aspirating, depositing, mixing, and transferring. Complex multistep operations for drug combination screening involving long-term cell culture, medium changing, schedule-dependent drug dosage and stimulation, and cell viability testing were achieved in parallel using the present system. The drug consumption for each screening test was substantially decreased to 5 ng-5 μg, corresponding to 10- to 1000-fold reductions compared with traditional drug screening systems with 96- or 384-well plates.
在过去几十年中，联合药物疗法已广泛应用于肿瘤学及其他复杂疾病的治疗。由于其具有降低药物毒性和提高治疗效果的潜在优势，联合药物治疗在基础实验室和制药公司中得到了越来越多的研究。在本章中，我们报告了基于顺序操作液滴阵列（SODA）技术的微流控液滴系统进行的基于细胞的联合药物筛选。在该系统中，一个油包二维液滴阵列芯片被用作细胞培养和分析的平台。该芯片固定在计算机程序控制的x-y-z平移台上。一个与注射泵相连的锥形毛细管与液滴阵列芯片耦合，以实现包括液体计量、抽吸、沉积、混合和转移在内的多种液滴操作。使用本系统可并行实现联合药物筛选中涉及长期细胞培养、更换培养基、依时间表给药和刺激以及细胞活力测试的复杂多步操作。每次筛选测试的药物消耗量大幅降低至5纳克至5微克，与使用96孔或384孔板的传统药物筛选系统相比，减少了10至1000倍。
