Abstract
Focusing and separation of cells by microfluidic techniques are significant steps in many applications, such as single-cell analysis and disease diagnosis. Among the microfluidic techniques, passive magnetophoresis, as a label-free manner, can manipulate samples by means of magnetic field. Nowadays, most magnetic fields are generated by permanent magnets and electromagnets with large size. However, it is difficult to assemble a magnetic array using permanent magnets or electromagnets to optimize the field distribution. To produce a flexible magnetic field, a micro-magnet made by NdFeB powder and polydimethyl siloxane is proposed in this paper, and those magnetized micro-magnets are arranged into different arrays according to the arrangements of their magnetization directions. Meanwhile, a microfluidic chip containing magnetized micro-magnet arrays is designed for focusing and separating polystyrene microbeads with different diameters. The focusing and separation behaviors of microbeads in the designed microfluidic system are numerical and experimental investigated. In addition, the effects of flow rate and the arrangement of the magnetic micro-magnet array on microbead focusing and separation are discussed. Finally, a multistage microfluidic chip is designed to successfully isolate 5 μm-diameter, 10 μm-diameter, and 15 μm-diameter microbeads from their mixture at a flow rate of 240 μL/min with high purity.
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig1_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig2_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig3_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig4_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig5_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig6_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig7_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig8_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig9_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig10_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig11_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig12_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig13_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig14_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig15_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig16_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig17_HTML.jpg)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig18_HTML.png)
![](http://media.springernature.com/m312/springer-static/image/art%3A10.1007%2Fs10404-024-02749-5/MediaObjects/10404_2024_2749_Fig19_HTML.jpg)
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
Alnaimat F, Dagher S, Mathew B, Hilal AH, Khashan S (2018) Microfluidics based magnetophoresis: a review. Chem Rec 18:1–18
Augustsson P, Magnusson C, Nordin M, Lilja H, Laurell T (2012) Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis. Anal Chem 84:7954–7962
Çetin B, Li D (2011) Dielectrophoresis in microfluidics technology. Electrophoresis 32:2410–2427
Chen P, Huang Y, Bhave G, Hoshino K, Zhang X (2015) Inkjet-print micromagnet array on glass slides for immunomagnetic enrichment of circulating tumor cells. Ann Biomed Eng 44(5):1710–1720
Chen S, Shi ZQ, Sun JJ, Jia SL, Zhong MJ, Ma YX (2022) High-throughput particle focusing and separation in split-recombination channel. J Micromech Microeng 32:025007
Chung YC, Wu CM, Lin SH (2016) Particles sorting in micro channel using designed micro electromagnets of magnetic field gradient. J Magn Magn Mater 407:209–217
Descamps L, Garcia J, Barthelemy D, Laurenceau E, Payen L, Roy DL, Deman AL (2022) MagPure chip: an immunomagnetic-based microfluidic device for high purification of circulating tumor cells from liquid biopsies. Lab Chip 22:4151–4166
Friedman G, Yellen B (2005) Magnetic separation, manipulation and assembly of solid phase in fluids. Curr Opin Colloid Interface Sci 10:158–166
Gijs MAM, Lacharme F, Lehmann U (2010) Microfluidic applications of magnetic particles for biological analysis and catalysis. Chem Rev 110:1518–1563
Gomez-Pastora J, Gonzalez-Fernandez C, Real E, Iles A, Bringas S, Furlani EP, Ortiz I (2018) Computational modeling and fluorescence microscopy characterization of a two-phase magnetophoretic microsystem for continuous-flow blood detoxification. Lab Chip 18:1593–1606
Huang Y, Chen P, Wu C, Hoshino K, Sokolov K, Lane N, Liu H, Huebschman M, Frenkel E, Zhang J (2015) Screening and molecular analysis of single circulating tumor cells using micromagnet array. Sci Rep 5:16047
Hyun KA, Lee TY, Lee SH, Jung HI (2015) Two-stage microfluidic chip for selective isolation of circulating tumor cells (CTCs). Biosens Bioelectron 67:86–92
Jokerst JC, Emory JM, Henry CS (2012) Advances in microfluidics for environmental analysis. Analyst 137:24–34
Kabacaoğlu G, Biros G (2019) Sorting same-size red blood cells in deep deterministic lateral displacement devices. J Fluid Mech 859:433–475
Khashan SA, Furlani EP (2013) Coupled particle–fluid transport and magnetic separation in microfluidic systems with passive magnetic functionality. J Phys D: Appl Phys 46:125002
Li P, Stratton ZS, Dao M, Ritz J, Huang T-J (2013) Probing circulating tumor cells in microfluidics. Lab Chip 13:602–609
Liang L, Zhang C, Xuan X (2013) Enhanced separation of magnetic and diamagnetic particles in a dilute ferrofluid. Appl Phys Lett 102:234101
Lim J, Yeap SP, Low SC (2014) Challenges associated to magnetic separation of nanomaterials at low field gradient. Sep Purif Technol 123:171–174
Lu X, Xuan X (2015) Inertia-enhanced pinched flow fractionation. Anal Chem 87:4560–4565
Marle L, Greenway GM (2005) Microfluidic devices for environmental monitoring. TrAC Trends Anal Chem 24:795–802
Maxey MR, Riley JJ (1983) Equation of motion for a small rigid sphere in a nonuniform flow. Phys Fluids 26:883–889
McGrath J, Imenez M, Bridle H (2014) Deterministic lateral displacement for particle separation: a review. Lab Chip 14:4139–4158
Merrin J (2019) Frontiers in microfluidics, a teaching resource review. Bioengineering 6:109
Munaz A, Shiddiky M, Nguyen NT (2018) Magnetophoretic separation of diamagnetic particles through parallel ferrofluid streams. Sens Actuators B Chem 275:459–469
Nilsson J, Evander M, Hammarstrom B, Laurell T (2009) Review of cell and particle trap** in microfluidic systems. Anal Chim Acta 649:141–157
Pachmann K, Camara O, Kavallaris A, Krauspe S, Malarski N, Gajda M, Kroll T, Jorke C, Hammer U, Altendorf-Hofmann A, Rabenstein C, Pachmann U, Runnebaum I, Hoffken K (2008) Monitoring the response of circulating epithelial tumor cells to adjuvant chemotherapy in breast cancer allows detection of patients at risk of early relapse. J Clin Oncol 26:1208–1215
Rosensweig RE (1987) Magnetic fluids. Ann Rev Fluid Mech 19:437–463
Samantaa A, Gangulyb R, Dattab A, Modak N (2017) Separation of magnetic beads in a hybrid continuous flow microfluidic device. J Magn Magn Mater 427:300–305
Shen YG, Yalikun Y, Tanaka Y (2019) Recent advances in microfluidic cell sorting systems. Sens Actuators B Chem 282:268–281
Shi ZQ, Chen S, Sun JJ, Li MJ, Jia SL (2020) Three-dimensional numerical analysis of focusing and separation of diamagnetic particles in ferrofluid. J Phys D: Appl Phys 53:315002
Shiriny A, Bayareh M (2020) On magnetophoretic separation of blood cells using halbach array of magnets. Meccanica 55:1903–1916
Suwa M, Watarai H (2011) Magnetoanalysis of micro/nanoparticles: a review. Anal Chim Acta 690:137–147
Tottori N, Nisisako T (2018) High-throughput production of satellite-free droplets through a parallelized microfluidic deterministic lateral displacement device. Sens Actuators B 206:918–926
Wu J, Cui Y, Xuan S, Gong X (2018) 3Dprinted microfluidic manipulation device integrated with magnetic array. Microfluid Nanofluid 22:103
Xu X, Huang X, Sun J, Wang R, Yao J, Han W, Wei M, Chen J, Guo J, Sun L, Yin L (2021) Recent progress of inertial microfluidic-based cell separation. Analyst 146:7070–7086
Yin H, Marshall D (2012) Microfluidics for single cell analysis. Curr Opin Biotechnol 23:110–119
Zeng J, Chen C, Vedantam P, Tzeng TR, Xuan XC (2013a) Magnetic concentration of particles and cells in ferrofluid flow through a straight microchannel using attracting magnets. Microfluid Nanofluid 15:49–55
Zeng J, Deng YX, Vedantam P, Tzeng TR, Xuan XC (2013b) Magnetic separation of particles and cells in ferrofluid flow through a straight microchannel using two offset magnets. J Magn Magn Mater 346:118–123
Zhou J, Papautsky I (2013) Fundamentals of inertial focusing in microchannels. Lab Chip 13:1121–1132
Zhou R, Wang C (2016a) Multiphase ferrofluid flows for micro-particle focusing and separation. Biomicrofluidics 10:034101
Zhou R, Wang C (2016b) Microfluidic separation of magnetic particles with soft magnetic microstructures. Microfluid Nanofluid 20:48
Zhu G, Nguyen NT (2012) Magnetofluidic spreading in microchannels. Microfluid Nanofluid 13:655–663
Zhu J, Liang L, Xuan X (2012) On-chip manipulation of nonmagnetic particles in paramagnetic solutions using embedded permanent magnets. Microfluid Nanofluid 12:65–73
Acknowledgements
The authors acknowledge financial support from the National Natural Science Foundation of China under project 52307015, the Fundamental Research Funds for the Central Universities under project sxzy012022014, and the Natural Science Foundation of Shaanxi Province under project 2023-JC-QN-0488.
Funding
National Natural Science Foundation of China, 52307015, Fundamental Research Funds for the Central Universities, sxzy012022014, Natural Science Foundation of Shaanxi Province, 2023-JC-QN-0488.
Author information
Authors and Affiliations
Contributions
S.C. and J.S. wrote the main manuscript text along with simulation, fabrication, and testing of the microfluidic device. Z.S., X.L. and K.W. revised and reviewed the manuscript. X.L., Y.M. and R.L. performed the experiments. S.X. and N.W. analyzed simulation data.
Corresponding authors
Ethics declarations
Conflict of interest
The authors state that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Chen, S., Sun, J., Shi, Z. et al. Investigation on the focusing and separation of polystyrene microbeads in an integrated microfluidic system using magnetized functionalized flexible micro-magnet arrays. Microfluid Nanofluid 28, 51 (2024). https://doi.org/10.1007/s10404-024-02749-5
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s10404-024-02749-5