Integrated Microfluidic Chip Design for Nucleic Acid Detection and Analysis of Droplet Manipulation
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摘要: 设计了一种基于磁珠法的两相流液滴微流控芯片,包含样品提纯、扩增和检测一系列连续的生化过程,可用于快速核酸检测。首先建立了磁珠和液滴在两相流体系内的动力学模型,并借助有限元仿真平台对磁珠微团所处环境进行了磁场仿真,得到不同体积磁珠微团所受的磁力。进一步还分析了磁珠微团、液滴体积、永磁体移动速度对液滴运动状态的影响,最终总结出液滴操纵图。Abstract: A two-phase flow droplet microfluidic chip based on magnetic bead method is designed in this paper, which includes a series of continuous biochemical processes for sample purification, amplification and detection, and this chip can be used for rapid nucleic acid detection. First, the dynamic models of magnetic beads and droplets in a two-phase flow system were established, and a magnetic field simulation was performed on the environment of the magnetic bead micelles by means of a finite element simulation platform to obtain the magnetic forces on the magnetic bead micelles of different volumes. Secondly, the three movement states of droplets of different volumes under the action of different volume of magnetic bead micelles are analyzed. Finally the relationship between the magnetic bead micelles, droplet volume and droplet movement is analyzed, and the droplet manipulation diagram is summarized.
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表 1 物理参数值
参数名 参数值 永磁体底面直径⌀/mm 1.5 永磁体高度h/mm 10 永磁体X方向剩余磁通密度Br/mT 0 永磁体Y方向剩余磁通密度Br/mT 0 永磁体Z方向剩余磁通密度Br/mT 500 真空磁导率μ0/(H·m-1) 4π×10-7 磁珠体积磁化率χ 0.29 油/水界面张力/(N·m-1) 0.051 磁珠微团球心距永磁体端部距离/mm 2 接触角θ/(°) 160 硅油粘度μoil/(Pa·s) 0.05 -
[1] 章春笋, 邢达. 连续流动式PCR微流控装置的研究[J]. 激光生物学报, 2007, 16(4): 501-508 doi: 10.3969/j.issn.1007-7146.2007.04.024ZHANG C S, XING D. A study on a continuous-flow PCR microfiuidics[J]. Acta Laser Biology Sinica, 2007, 16(4): 501-508 (in Chinese) doi: 10.3969/j.issn.1007-7146.2007.04.024 [2] JEONG O C, KONISHI S. Fabrication of a peristaltic micro pump with novel cascaded actuators[J]. Journal of Micromechanics and Microengineering, 2008, 18(2): 025022 doi: 10.1088/0960-1317/18/2/025022 [3] QIAN J Y, CHEN M R, LIU X L, et al. A numerical investigation of the flow of nanofluids through a micro Tesla valve[J]. Journal of Zhejiang University-Science A (Applied Physics & Engineering), 2019, 20(1): 50-60 doi: 10.1631/jzus.A1800431.pdf [4] SOLVAS X C I, DEMELLO A. Droplet microfluidics: recent developments and future applications[J]. Chemical Communications, 2011, 47(7): 1936-1942 doi: 10.1039/C0CC02474K [5] TEH S Y, LIN R, HUNG L H, et al. Droplet microfluidics[J]. Lab on A Chip, 2008, 8(2): 198-220 doi: 10.1039/b715524g [6] SHI X, CHEN C H, GAO W M, et al. Parallel RNA extraction using magnetic beads and a droplet array[J]. Lab on a Chip, 2015, 15(4): 1059-1065 doi: 10.1039/C4LC01111B [7] WANG Y Z, ZHAO Y J, CHO S K. In-droplet magnetic beads concentration and separation for digital microfluidics[C]//TRANSDUCERS 2007-2007 International Solid-State Sensors, Actuators and Microsystems Conference. Lyon: IEEE, 2007: 711-714 [8] 曾一笑, 樊磊, 吴菲, 等. 基于介电电泳的粒子分离微流控芯片的研究[J]. 仪表技术与传感器, 2017(2): 5-8, 14 doi: 10.3969/j.issn.1002-1841.2017.02.002ZENG Y X, FAN L, WU F, et al. Study on particle separation of microfluidic chip based on dielectrophoresis[J]. Instrument Technique and Sensor, 2017(2): 5-8, 14 (in Chinese) doi: 10.3969/j.issn.1002-1841.2017.02.002 [9] FORNELL A, OHLIN M, GAROFALO F, et al. An intra-droplet particle switch for droplet microfluidics using bulk acoustic waves[J]. Biomicrofluidics, 2017, 11(3): 031101 doi: 10.1063/1.4984131 [10] GUCKENBERGER D J, PEZZI H M, REGIER M C, et al. Magnetic system for automated manipulation of paramagnetic particles[J]. Analytical Chemistry, 2016, 88(20): 9902-9907 doi: 10.1021/acs.analchem.6b02257 [11] DEN DULK R C, SCHMIDT K A, SABATTÉ G, et al. Magneto-capillary valve for integrated purification and enrichment of nucleic acids and proteins[J]. Lab on a Chip, 2012, 13(1): 106-118 http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM23128479 [12] BORDELON H, BIRIS A S, SABLIOV C M, et al. Characterization of plasmid DNA location within chitosan/PLGA/pDNA nanoparticle complexes designed for gene delivery[J]. Journal of Nanomaterials, 2011, 2011: 952060 https://www.hindawi.com/journals/jnm/2011/952060/ [13] YANG C, LI G. A novel magnet-actuated droplet manipula-tion platform using a floating ferrofluid film[J]. Scientific Reports, 2017, 7(1): 15705 doi: 10.1038/s41598-017-15964-8 [14] BUSCH-VISHNIAC I J. The case for magnetically driven microactuators[J]. Sensors and Actuators A: Physical, 1992, 33(3): 207-220 doi: 10.1016/0924-4247(92)80168-3 [15] RIDA A, FERNANDEZ V, GIJS M A M. Long-range transport of magnetic microbeads using simple planar coils placed in a uniform magnetostatic field[J]. Applied Physics Letters, 2003, 83(12): 2396 doi: 10.1063/1.1613038 [16] STROHMEIER O, EMPERLE A, ROTH G, et al. Centrifugal gas-phase transition magnetophoresis (GTM)-a generic method for automation of magnetic bead based assays on the centrifugal microfluidic platform and application to DNA purification[J]. Lab on a Chip, 2012, 13(1): 146-155 http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_PM23142800 [17] KIM H Y, LEE H J, KANG B H. Sliding of liquid drops down an inclined solid surface[J]. Journal of Colloid and Interface Science, 2002, 247(2): 372-380 doi: 10.1006/jcis.2001.8156