北京生物医学工程

一种高通量测量单细胞弹性模量的微流控芯片

A high-throughput microfluidic chip for trapping single cells and measuring single cells’ elastic moduli

作者：袁闱墨薛春东刘波覃开蓉

单位：大连理工大学电子信息与电气工程学部生物医学工程学院( 辽宁大连 116024) 大连理工大学光电工程与仪器科学学院( 辽宁大连 116024)

关键词：微流控; 芯片实验室; 有限元分析; 生物力学

分类号： R318.6

出版年·卷·期（页码）：2019·38·5（450-456）

摘要：

目的设计微流控芯片以便高效简便地捕获大量单细胞并测量其弹性模量。方法根据流体力学原理，设计微流控阵列及其单细胞捕获单元的通道结构和几何尺寸。培养海拉细胞，制作微流控芯片实物并采用该芯片进行单细胞捕获实验。采用COMSOL软件对作用在被捕获细胞上的剪切力和压差进行有限元仿真。根据作用在被捕获细胞两侧的压差值和细胞在捕获通道中的伸长长度，计算出细胞的弹性模量。结果所设计的微流控芯片能有效捕获大量单细胞；计算的单细胞弹性模量为780.7Pa ± 100.5 Pa，与文献中报道的763Pa ± 93 Pa接近。结论本文所提出的微流控芯片可高效捕获单细胞并测量单细胞力学特性。

Objective To design a microfluidic chip to efficiently and conveniently trap substantial single cells and measure single cells’ elastic moduli. Method Based on the principle of fluid mechanics, a microfluidic array and the structure and geometrical size of its single cell trapping unit were designed. Hela cells were cultured and maintained, the actual microfluidic chip was then fabricated to conduct the single cells trapping experiment. By using software COMSOL, finite element simulation was conducted to compute the shear stress and pressure drop across the trapped cells. The single cells’ elastic moduli were computed by the pressure drops across the trapped single cells and the cellular protrusion lengths in the trapping channels. Results Many single cells were able to be efficiently trapped in the microfluidic chip. The computed elastic moduli of single cells were 780.7 Pa± 100.5 Pa, which were close to the moduli 763Pa ± 93 Pa reported in the literature. Conclusions The microfluidic chip proposed in this study exhibites a high efficiency for single cells trapping and measurement of single cellular mechanical property.

参考文献：

[1] Pachenari M, Seyedpour SM, Janmaleki M, et al. Mechanical properties of cancer cytoskeleton depend on actin filaments to microtubules content: Investigating different grades of colon cancer cell lines[J]. Journal of Biomechanics, 2014, 47(2):373-379.

[2] Jing PF, Liu YN, Keeler EG, et al. Optical tweezers system for live stem cell organization at the single-cell level[J]. Biomedical Optics Express, 2018, 9(2):771–779.

[3] Hochmuth RM. Micropipette aspiration of living cells[J]. Journal of Biomechanics, 2000, 33(1):15-22.

[4] Lange JR, Metzner C, Richter S, et al. Unbiased High-Precision Cell Mechanical Measurements with Microconstrictions[J]. Biophysical Journal, 2017, 112(7):1472-1480.

[5] Li YJ, Yang YN, Zhang HJ, et al. A microfluidic micropipette aspiration device to study single-cell mechanics inspired by the principle of wheatstone bridge[J]. Micromachines, 2019, 10(2):131–142.

[6] Guo Q, Park S, Ma H. Microfluidic micropipette aspiration for measuring the deformability of single cells[J]. Lab on a Chip, 2012, 12(15):2687–2695.

[7] Lee LM, Liu AP. A microfluidic pipette array for mechanophenotyping of cancer cells and mechanical gating of mechanosensitive channels[J]. Lab on a Chip, 2014, 15.

[8] Czerwinska J, Pumpurus L, Rieger M, et al. Mobility and shape adaptation of neutrophil in the microchannel flow[J]. Journal of the Mechanical Behavior of Biomedical Materials, 2017, 69(Complete):294-300.

[9] Deng Y, Davis SP, Yang F, et al. Inertial Micro?uidic Cell Stretcher (iMCS): Fully automated,

high-throughput, and near real-time cell mechanotyping[J]. Small, 2017:1700705.

[10] Yu M, Hou Y, Song R, et al. Tunable confinement for bridging single-cell manipulation and single-molecule DNA linearization[J]. Small, 2018:1800229.

[11] Narayanamurthy V, Nagarajan S, Khan AYF, et al. Microfluidic hydrodynamic trapping for single cell analysis: mechanisms, methods and applications[J]. Analytical Methods, 2017, 9(25):3751–3772.

[12] Tan WH, Takeuchi S. A Trap-and-release Integrated microfluidic system for dynamic microarray applications[J]. Proceedings of the National Academy of Sciences, 2007, 104(4):1146-1151.

[13] Kobel S, Valero A, Latt J, et al. Optimization of microfluidic single cell trapping for long-term on-chip culture[J]. Lab on a Chip, 2010, 10(7):857.

[14] Lawrenz A, Nason F, Cooper-White JJ. Geometrical effects in microfluidic-based microarrays for rapid, efficient single-cell capture of mammalian stem cells and plant cells[J]. Biomicrofluidics, 2012, 6(2):433-441.

[15] 王雪莉, 钱翔, 谢振华, 等. 基于微流控芯片的姜黄素诱导MCF－7细胞凋亡的研究[J]. 北京生物医学工程, 2011, 30(6):557–561.

Microfluidic chip-based apoptosis of MCF －7 induced by curcumin[J]. Beijing Biomedical Engineering, 2011, 30(6):557–561.

[16] Theret DP, Levesque MJ, Sato M, et al. The Application of a Homogeneous Half-Space Model in the Analysis of Endothelial Cell Micropipette Measurements[J]. Journal of Biomechanical Engineering, 1988, 110(3):190.

[17] Raj A , Dixit M , Doble M , et al. A combined experimental and theoretical approach towards mechano-phenotyping of biological cells using a constricted microchannel[J]. Lab on a Chip, 2017, 17(21):3704–3716.

服务与反馈：

【文章下载】【加入收藏】

提示：您还未登录，请登录！点此登录