Sohrabi Salman, Tan Jifu, Yunus Doruk Erdem, He Ran, Liu Yaling
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.
Department of Mechanical Engineering, Northern Illinois University, DeKalb, Illinois 60115, USA.
Biomicrofluidics. 2018 May 21;12(4):042206. doi: 10.1063/1.5022500. eCollection 2018 Jul.
Isolating cells of interest from a heterogeneous population has been of critical importance in biological studies and clinical applications. In this study, a novel approach is proposed for utilizing an active ciliary system in microfluidic devices to separate particles based on their physical properties. In this approach, the bottom of the microchannel is covered with an equally spaced cilia array of various patterns which is actuated by an external stimuli. 3D simulations are carried out to study cilia-particle interaction and isolation dynamic in a microfluidic channel. It is observed that these elastic hair-like filaments can influence particle's trajectories differently depending on their biophysical properties. This modeling study utilizes immersed boundary method coupled with the lattice Boltzmann method. Soft particles and cilia are implemented through the spring connected network model and point-particle scheme, respectively. It is shown that cilia array with proper stimulation is able to continuously and non-destructively separate cells into subpopulations based on their size, shape, and stiffness. At the end, a design map for fabrication of a programmable microfluidic device capable of isolating various subpopulations of cells is developed. This biocompatible, label-free design can separate cells/soft microparticles with high throughput which can greatly complement existing separation technologies.
从异质群体中分离出感兴趣的细胞在生物学研究和临床应用中一直至关重要。在本研究中，提出了一种利用微流控装置中的主动纤毛系统根据颗粒的物理性质分离颗粒的新方法。在这种方法中，微通道底部覆盖有由外部刺激驱动的各种图案的等间距纤毛阵列。进行了三维模拟以研究微流控通道中的纤毛 - 颗粒相互作用和分离动力学。观察到这些弹性毛发状细丝可以根据颗粒的生物物理性质以不同方式影响颗粒的轨迹。该建模研究利用浸入边界法与格子玻尔兹曼法相结合。软颗粒和纤毛分别通过弹簧连接网络模型和点粒子方案实现。结果表明，具有适当刺激的纤毛阵列能够基于细胞的大小、形状和刚度将细胞连续且无损地分离成亚群。最后，开发了一种用于制造能够分离各种细胞亚群的可编程微流控装置的设计图。这种生物相容性、无标记的设计可以高通量分离细胞/软微粒，这可以极大地补充现有的分离技术。
