Graduate Institute of Biochemical and Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
Lab Chip. 2010 Apr 21;10(8):939-56. doi: 10.1039/b921695b. Epub 2010 Jan 21.
In pharmaceutical research, an adequate cell-based assay scheme to efficiently screen and to validate potential drug candidates in the initial stage of drug discovery is crucial. In order to better predict the clinical response to drug compounds, a cell culture model that is faithful to in vivo behavior is required. With the recent advances in microfluidic technology, the utilization of a microfluidic-based cell culture has several advantages, making it a promising alternative to the conventional cell culture methods. This review starts with a comprehensive discussion on the general process for drug discovery and development, the role of cell culture in drug research, and the characteristics of the cell culture formats commonly used in current microfluidic-based, cell-culture practices. Due to the significant differences in several physical phenomena between microscale and macroscale devices, microfluidic technology provides unique functionality, which is not previously possible by using traditional techniques. In a subsequent section, the niches for using microfluidic-based cell culture systems for drug research are discussed. Moreover, some critical issues such as cell immobilization, medium pumping or gradient generation in microfluidic-based, cell-culture systems are also reviewed. Finally, some practical applications of microfluidic-based, cell-culture systems in drug research particularly those pertaining to drug toxicity testing and those with a high-throughput capability are highlighted.
在药物研究中,需要建立一个充分的基于细胞的检测方案,以便在药物发现的初始阶段有效地筛选和验证潜在的药物候选物。为了更好地预测药物化合物的临床反应,需要使用一种与体内行为相符的细胞培养模型。随着微流控技术的最新进展,基于微流控的细胞培养具有几个优点,使其成为传统细胞培养方法的有前途的替代方法。这篇综述首先全面讨论了药物发现和开发的一般过程、细胞培养在药物研究中的作用,以及当前基于微流控的细胞培养实践中常用的细胞培养格式的特点。由于微尺度和宏观尺度设备之间存在若干物理现象的显著差异,微流控技术提供了独特的功能,这是传统技术以前无法实现的。在随后的部分中,讨论了使用基于微流控的细胞培养系统进行药物研究的优势。此外,还回顾了基于微流控的细胞培养系统中的一些关键问题,如细胞固定化、介质泵送或微通道内的梯度生成。最后,突出了基于微流控的细胞培养系统在药物研究中的一些实际应用,特别是那些与药物毒性测试和高通量能力相关的应用。