High-throughput cell cycle synchronization using inertial forces in spiral microchannels
High-throughput cell cycle synchronization using inertial forces in spiral microchannels
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DOI：
10.1039/c0lc00579g
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发表时间：
2011-01-01
期刊：
影响因子：
6.1
通讯作者：
Lim, Chwee Teck
中科院分区：
文献类型：
--
作者：
Lee, Wong Cheng;Bhagat, Ali Asgar S.;Lim, Chwee Teck
在细胞复制周期的不同阶段对细胞进行有效的同步化和选择有助于基础研究和细胞周期靶向疗法的开发。目前基于化学的同步方法是不利的，因为这些方法会破坏细胞生理和代谢。为物理细胞分离开发的微流体系统提供了传统细胞同步方法的潜在替代方案。在这里，我们介绍了一个螺旋微流控装置的细胞周期同步，利用惯性力和迪恩阻力的综合作用。通过利用细胞直径和细胞周期（DNA含量/倍性）之间的关系，我们已经成功地将几种异步哺乳动物细胞系以及包括骨髓来源的人间充质干细胞（hMSC）的原代细胞分级为G 0/G1（> 85%）、S和G2/M期的富集亚群。这种细胞周期富集水平与现有的微流体系统相当，但由此同步的细胞的通量（类似于15 × 10（6）个细胞/h）和活力（类似于95%）显著更大。此外，该平台提供了同步细胞或分离后直径分选细胞的快速收集，以实现细胞增殖研究和操作中的多种应用。
Efficient synchronization and selection of cells at different stages of the cell replication cycle facilitates both fundamental research and development of cell cycle-targeted therapies. Current chemical-based synchronization methods are unfavorable as these can disrupt cell physiology and metabolism. Microfluidic systems developed for physical cell separation offer a potential alternative over conventional cell synchronization approaches. Here we introduce a spiral microfluidic device for cell cycle synchronization, using the combined effects of inertial forces and Dean drag force. By exploiting the relationship between cell diameter and cell cycle (DNA content/ploidy), we have successfully fractionated several asynchronous mammalian cell lines, as well as primary cells comprising bone marrow-derived human mesenchymal stem cells (hMSCs), into enriched subpopulations of G0/G1 (> 85%), S, and G2/M phases. This level of cell cycle enrichment is comparable to existing microfluidic systems, but the throughput (similar to 15 x 10(6) cells per h) and viability (similar to 95%) of cells thus synchronized are significantly greater. Further, this platform provides rapid collection of synchronized cells or of diameter-sorted cells post-separation, to enable diverse applications in the study and manipulation of cell proliferation.