Lee Lap Man, Lee Jin Woo, Chase Danielle, Gebrezgiabhier Daniel, Liu Allen P
Department of Mechanical Engineering, University of Michigan , Ann Arbor, Michigan 48109, USA.
Department of Mechanical Engineering, University of Minnesota , Twin Cities, Minnesota 55455, USA.
Biomicrofluidics. 2016 Sep 20;10(5):054105. doi: 10.1063/1.4962968. eCollection 2016 Sep.
Various micro-engineered tools or platforms have been developed recently for cell mechanics studies based on acoustic, magnetic, and optical actuations. Compared with other techniques for single cell manipulations, microfluidics has the advantages with simple working principles and device implementations. In this work, we develop a multi-layer microfluidic pipette aspiration device integrated with pneumatically actuated microfluidic control valves. This configuration enables decoupling of cell trapping and aspiration, and hence causes less mechanical perturbation on trapped single cells before aspiration. A high trapping efficiency is achieved by the microfluidic channel design based on fluid resistance model and deterministic microfluidics. Compared to conventional micropipette aspiration, the suction pressure applied on the aspirating cells is highly stable due to the viscous nature of low Reynolds number flow. As a proof-of-concept of this novel microfluidic technology, we built a microfluidic pipette aspiration device with 2 × 13 trapping arrays and used this device to measure the stiffness of a human breast cancer cell line, MDA-MB-231, through the observation of cell deformations during aspiration. As a comparison, we studied the effect of Taxol, a FDA-approved anticancer drug on single cancer cell stiffness. We found that cancer cells treated with Taxol were less deformable with a higher Young's modulus. The multi-layer microfluidic pipette aspiration device is a scalable technology for single cell mechanophenotyping studies and drug discovery applications.
最近，人们基于声学、磁学和光学驱动开发了各种微工程工具或平台用于细胞力学研究。与其他单细胞操作技术相比，微流控技术具有工作原理和设备实现简单的优点。在这项工作中，我们开发了一种集成了气动微流控控制阀的多层微流控移液管抽吸装置。这种配置能够实现细胞捕获和抽吸的解耦，从而在抽吸之前对捕获的单细胞造成较小的机械扰动。基于流体阻力模型和确定性微流控的微流控通道设计实现了高捕获效率。与传统的微量移液管抽吸相比，由于低雷诺数流动的粘性特性，施加在抽吸细胞上的抽吸压力高度稳定。作为这种新型微流控技术的概念验证，我们构建了一个具有2×13捕获阵列的微流控移液管抽吸装置，并使用该装置通过观察抽吸过程中的细胞变形来测量人乳腺癌细胞系MDA-MB-231的刚度。作为比较，我们研究了美国食品药品监督管理局批准的抗癌药物紫杉醇对单个癌细胞刚度的影响。我们发现，用紫杉醇处理的癌细胞变形性较小，杨氏模量较高。多层微流控移液管抽吸装置是一种用于单细胞机械表型研究和药物发现应用的可扩展技术。
