Department of Applied Physics, University of Michigan, Ann Arbor, Michigan, United States of America.
PLoS One. 2011;6(12):e28475. doi: 10.1371/journal.pone.0028475. Epub 2011 Dec 13.
Single cell analysis has allowed critical discoveries in drug testing, immunobiology and stem cell research. In addition, a change from two to three dimensional growth conditions radically affects cell behavior. This already resulted in new observations on gene expression and communication networks and in better predictions of cell responses to their environment. However, it is still difficult to study the size and shape of single cells that are freely suspended, where morphological changes are highly significant. Described here is a new method for quantitative real time monitoring of cell size and morphology, on single live suspended cancer cells, unconfined in three dimensions. The precision is comparable to that of the best optical microscopes, but, in contrast, there is no need for confining the cell to the imaging plane. The here first introduced cell magnetorotation (CM) method is made possible by nanoparticle induced cell magnetization. By using a rotating magnetic field, the magnetically labeled cell is actively rotated, and the rotational period is measured in real-time. A change in morphology induces a change in the rotational period of the suspended cell (e.g. when the cell gets bigger it rotates slower). The ability to monitor, in real time, cell swelling or death, at the single cell level, is demonstrated. This method could thus be used for multiplexed real time single cell morphology analysis, with implications for drug testing, drug discovery, genomics and three-dimensional culturing.
单细胞分析在药物测试、免疫生物学和干细胞研究方面取得了重要发现。此外,从二维到三维的生长条件的改变极大地影响了细胞的行为。这已经导致了对基因表达和通信网络的新观察,并更好地预测了细胞对其环境的反应。然而,对于自由悬浮的单细胞的大小和形状的研究仍然很困难,因为形态变化非常显著。本文介绍了一种新的方法,用于定量实时监测在三维无约束条件下自由悬浮的活癌细胞的大小和形态。其精度可与最好的光学显微镜相媲美,但与光学显微镜不同的是,不需要将细胞限制在成像平面内。这里首次引入的细胞磁旋转(CM)方法是通过纳米颗粒诱导细胞磁化实现的。通过使用旋转磁场,可主动旋转标记有磁性的细胞,并实时测量旋转周期。悬浮细胞的形态变化会引起旋转周期的变化(例如,当细胞变大时,它的旋转速度会变慢)。证明了能够实时监测单细胞的肿胀或死亡。因此,该方法可用于多重实时单细胞形态分析,在药物测试、药物发现、基因组学和三维培养方面具有应用前景。