Microfluidics and Nanofluidics

, Volume 13, Issue 4, pp 613–623 | Cite as

Continuous-flow in-droplet magnetic particle separation in a droplet-based microfluidic platform

  • Hun Lee
  • Linfeng Xu
  • Byungwook Ahn
  • Kangsun Lee
  • Kwang W. OhEmail author
Research Paper


This paper presents a continuous-flow in-droplet magnetic particle separation in a droplet-based microfluidic device for magnetic bead-based bioassays. Two functions, electrocoalescence and magnetic particle manipulation, are performed in this device. A pair of charging metallic needles is inserted into two aqueous channels of the device. By electrostatic force, two different solutions can be merged to be mixed at a junction of droplet generation. The manipulation of magnetic particles is achieved using an externally applied magnetic field. The magnetic particles are separated by the magnetic field to one side of the droplet and extracted by splitting the droplet into two daughter droplets: one contains the majority of the magnetic particles and the other is almost devoid of magnetic particles. The applicability of the continuous-flow in-droplet magnetic particle separation is demonstrated by performing a proof-of-concept immunoassay between streptavidin-coated magnetic beads and biotin labelled with fluorescence. This approach will be useful for various biological and chemical analyses and compartmentalization of small samples.


Magnetic particle manipulation Magnetic field Magnetic bead assay Droplet merging Droplet splitting 



This work was supported by the National Science Foundation grants (Grant Nos. ECCS-1002255 and ECCS-0736501).


  1. Ahn K, Agresti J, Chong H, Marquez M, Weitz DA (2006) Electrocoalescence of drops synchronized by size-dependent flow in microfluidic channels. Appl Phys Lett 88:264105–264107CrossRefGoogle Scholar
  2. Ahn B, Lee K, Lee H, Panchapakesan R, Oh KW (2011) Parallel synchronization of two trains of droplets using a railroad-like channel network. Lab Chip 11:3956–3962CrossRefGoogle Scholar
  3. Auroux PA, Iossifidis D, Reyes DR, Manz A (2002) Micro total analysis systems. 2. Analytical standard operations and applications. Anal Chem 74:2637–2652CrossRefGoogle Scholar
  4. Beebe DJ, Mensing GA, Walker GM (2002) Physics and applications of microfluidics in biology. Annu Rev Biomed Eng 4:261–286CrossRefGoogle Scholar
  5. Blankenstein G, Larsen UD (1998) Modular concept of a laboratory on a chip for chemical and biochemical analysis. Biosens Bioelectron 13:427–438CrossRefGoogle Scholar
  6. Bringer MR, Gerdts CJ, Song H, Tice JD, Ismagilov RF (2004) Microfluidic systems for chemical kinetics that rely on chaotic mixing in droplets. Philos T Roy Soc A 362:1087–1104CrossRefGoogle Scholar
  7. Choi JW, Oh KW, Thomas JH, Heineman WR, Halsall HB, Nevin JH, Helmicki AJ, Henderson HT, Ahn CH (2002) An integrated microfluidic biochemical detection system for protein analysis with magnetic bead-based sampling capabilities. Lab Chip 2:27–30CrossRefGoogle Scholar
  8. Cohen DE, Schneider T, Wang M, Chiu DT (2010) Self-digitization of sample volumes. Anal Chem 82:5707–5717CrossRefGoogle Scholar
  9. Fan ZH, Mangru S, Granzow R, Heaney P, Ho W, Dong QP, Kumar R (1999) Dynamic DNA hybridization on a chip using paramagnetic beads. Anal Chem 71:4851–4859CrossRefGoogle Scholar
  10. Gu H, Duits MHG, Mugele F (2011) Droplets formation and merging in two-phase flow microfluidics. Int J Mol Sci 12:2572–2597CrossRefGoogle Scholar
  11. Ismagilov RF (2003) Integrated microfluidic systems. Angew Chem Int Edit 42:4130–4132CrossRefGoogle Scholar
  12. Jemere AB, Oleschuk RD, Ouchen F, Fajuyigbe F, Harrison DJ (2002) An integrated solid-phase extraction system for sub-picomolar detection. Electrophoresis 23:3537–3544CrossRefGoogle Scholar
  13. Jeong Y, Choi K, Kim J, Chung DS, Kim B, Kim HC, Chun K (2008) PDMS micro bead cage reactor for the detection of alpha feto protein (AFP). Sensor Actuat B-Chem 128:349–358CrossRefGoogle Scholar
  14. Kim KS, Park JK (2005) Magnetic force-based multiplexed immunoassay using superparamagnetic nanoparticles in microfluidic channel. Lab Chip 5:657–664CrossRefGoogle Scholar
  15. Kinoshita H, Kaneda S, Fujii T, Oshima M (2007) Three-dimensional measurement and visualization of internal flow of a moving droplet using confocal micro-PIV. Lab Chip 7:338–346CrossRefGoogle Scholar
  16. Kohler JM, Henkel T, Grodrian A, Kirner T, Roth M, Martin K, Metze J (2004) Digital reaction technology by micro segmented flow—components, concepts and applications. Chem Eng J 101:201–216CrossRefGoogle Scholar
  17. Lombardi D, Dittrich PS (2011) Droplet microfluidics with magnetic beads: a new tool to investigate drug-protein interactions. Anal Bioanal Chem 399:347–352CrossRefGoogle Scholar
  18. Lorenz RM, Edgar JS, Jeffries GDM, Chiu DT (2006) Microfluidic and optical systems for the on-demand generation and manipulation of single femtoliter-volume aqueous droplets. Anal Chem 78:6433–6439CrossRefGoogle Scholar
  19. Nolan JP, Sklar LA (2002) Suspension array technology: evolution of the flat-array paradigm. Trends Biotechnol 20:9–12CrossRefGoogle Scholar
  20. Pamme N (2007) Continuous flow separations in microfluidic devices. Lab Chip 7:1644–1659CrossRefGoogle Scholar
  21. Pamme N, Manz A (2004) On-chip free-flow magnetophoresis: continuous flow separation of magnetic particles and agglomerates. Anal Chem 76:7250–7256CrossRefGoogle Scholar
  22. Pamme N, Wilhelm C (2006) Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis. Lab Chip 6:974–980CrossRefGoogle Scholar
  23. Peyman SA, Iles A, Pamme N (2009) Mobile magnetic particles as solid-supports for rapid surface-based bioanalysis in continuous flow. Lab Chip 9:3110–3117CrossRefGoogle Scholar
  24. Priest C, Herminghaus S, Seemann R (2006) Controlled electrocoalescence in microfluidics: targeting a single lamella. Appl Phys Lett 89:134101–134103CrossRefGoogle Scholar
  25. Rodriguez-Villareal AI, Tarn MD, Madden LA, Lutz JB, Greenman J, Samitier J, Pamme N (2011) Flow focusing of particles and cells based on their intrinsic properties using a simple diamagnetic repulsion setup. Lab Chip 11:1240–1248CrossRefGoogle Scholar
  26. Schwartz JA, Vykoukal JV, Gascoyne PRC (2004) Droplet-based chemistry on a programmable micro-chip. Lab Chip 4:11–17CrossRefGoogle Scholar
  27. Siegel AC, Shevkoplyas SS, Weibel DB, Bruzewicz DA, Martinez AW, Whitesides GM (2006) Cofabrication of electromagnets and microfluidic systems in poly(dimethylsiloxane). Angew Chem Int Edit 45:6877–6882CrossRefGoogle Scholar
  28. Tan YC, Fisher JS, Lee AI, Cristini V, Lee AP (2004) Design of microfluidic channel geometries for the control of droplet volume, chemical concentration, and sorting. Lab Chip 4:292–298CrossRefGoogle Scholar
  29. Tan YC, Ho YL, Lee AP (2007) Droplet coalescence by geometrically mediated flow in microfluidic channels. Microfluid Nanofluid 3:495–499CrossRefGoogle Scholar
  30. Tsai SSH, Griffiths IM, Stone HA (2011) Microfluidic immunomagnetic multi-target sorting—a model for controlling deflection of paramagnetic beads. Lab Chip 11:2577–2582CrossRefGoogle Scholar
  31. Wang C, Oleschuk R, Ouchen F, Li JJ, Thibault P, Harrison DJ (2000) Integration of immobilized trypsin bead beds for protein digestion within a microfluidic chip incorporating capillary electrophoresis separations and an electrospray mass spectrometry interface. Rapid Commun Mass Spectrom 14:1377–1383CrossRefGoogle Scholar
  32. Ward T, Faivre M, Abkarian M, Stone HA (2005) Microfluidic flow focusing: drop size and scaling in pressure versus flow-rate-driven pumping. Electrophoresis 26:3716–3724Google Scholar
  33. Xia YN, Whitesides GM (1998) Soft lithography. Annu Rev Mater Sci 28:153–184CrossRefGoogle Scholar
  34. Yung CW, Fiering J, Mueller AJ, Ingber DE (2009) Micromagnetic-microfluidic blood cleansing device. Lab Chip 9:1171–1177CrossRefGoogle Scholar
  35. Zagnoni M, Cooper JM (2009) On-chip electrocoalescence of microdroplets as a function of voltage, frequency and droplet size. Lab Chip 9:2652–2658CrossRefGoogle Scholar
  36. Zborowski M, Fuh CB, Green R, Sun LP, Chalmers JJ (1995) Analytical magnetapheresis of ferritin-labeled lymphocytes. Anal Chem 67:3702–3712CrossRefGoogle Scholar
  37. Zheng B, Ismagilov RF (2005) A microfluidic approach for screening submicroliter volumes against multiple reagents by using preformed arrays of nanoliter plugs in a three-phase liquid/liquid/gas flow. Angew Chem Int Edit 44:2520–2523CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Hun Lee
    • 1
  • Linfeng Xu
    • 1
  • Byungwook Ahn
    • 1
  • Kangsun Lee
    • 1
  • Kwang W. Oh
    • 1
    Email author
  1. 1.SMALL (Sensors and MicroActuators Learning Laboratory), Department of Electrical EngineeringUniversity at Buffalo, The State University of New York (SUNY at Buffalo)BuffaloUSA

Personalised recommendations