Skip to main content
Log in

Inertial Microfluidics-Based Cell Sorting

  • Review Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Inertial microfluidics has attracted significant attention in recent years due to its superior benefits of high throughput, precise control, simplicity, and low cost. Many inertial microfluidic applications have been demonstrated for physiological sample processing, clinical diagnostics, and environmental monitoring and cleanup. In this review, we discuss the fundamental mechanisms and principles of inertial migration and Dean flow, which are the basis of inertial microfluidics, and provide basic scaling laws for designing the inertial microfluidic devices. This will allow end-users with diverse backgrounds to more easily take advantage of the inertial microfluidic technologies in a wide range of applications. A variety of recent applications are also classified according to the structure of the microchannel: straight channels and curved channels. Finally, several future perspectives of employing fluid inertia in microfluidic-based cell sorting are discussed. Inertial microfluidics is still expected to be promising in the near future with more novel designs using various shapes of cross section, sheath flows with different viscosities, or technologies that target micron and submicron bioparticles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yu, Z.T.F., Yong, K.M.A. & Fu, J. Microfluidic blood cell sorting: now and beyond. Small 10, 1687–1703 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wyatt Shields IV, C., Reyes, C. & López, G.P. Microfluidic cell sorting: a review of the advances in the separation of cells from debulking to rare cell isolation. Lab Chip 15, 1230–1249 (2015).

    Article  CAS  PubMed  Google Scholar 

  3. Antfolk, M. & Laurell, T. Continuous flow microfluidic separation and processing of rare cells and bioparticles found in blood-a review. Anal. Chim. Acta 965, 9–35 (2017).

    Article  CAS  PubMed  Google Scholar 

  4. Wu, J., Chen, Q. & Lin, J.-M. Microfluidic technologies in cell isolation and analysis for biomedical applications. Analyst 142, 421–441 (2017).

    Article  CAS  PubMed  Google Scholar 

  5. Mao, X., Lin, S.-C.S., Dong, C. & Huang, T.J. Singlelayer planar on-chip flow cytometer using microfluidic drifting based three-dimensional (3D) hydrodynamic focusing. Lab Chip 9, 1583–1589 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Lin, S.-C., Yen, P.-W., Peng, C.-C. & Tung, Y.-C. Single channel layer, single sheath-flow inlet microfluidic flow cytometer with three-dimensional hydrodynamic focusing. Lab Chip 12, 3135–3141 (2012).

    Article  CAS  PubMed  Google Scholar 

  7. Mach, A.J., Adeyiga, O.B. & Di Carlo, D. Microfluidic sample preparation for diagnostic cytopathology. Lab Chip 13, 1011–1026 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Li, X., Chen, W., Liu, G., Lu, W. & Fu, J. Continuousflow microfluidic blood cell sorting for unprocessed whole blood using surface-micromachined microfiltration membranes. Lab Chip 14, 2565–2575 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tripathi, S., Kumar, Y.V.B., Agrawal, A., Prabhakar, A. & Joshi, S.S. Microdevice for plasma separation from whole human blood using bio-physical and geometrical effects. Sci. Rep. 6, 26749 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Myung, J.H. & Hong, S. Microfluidic devices to enrich and isolate circulating tumor cells. Lab Chip 15, 4500–4511 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Yeo, T. et al. Microfluidic enrichment for the single cell analysis of circulating tumor cells. Sci. Rep. 6, 22076 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Doh, I. & Cho, Y.-H. A continuous cell separation chip using hydrodynamic dielectrophoresis (DEP) process. Sens. Actuators A Phys. 121, 59–65 (2005). https://doi. org/10.1016/j.sna.2005.01.030

    Article  CAS  Google Scholar 

  13. Çetin, B. & Li, D. Dielectrophoresis in microfluidics technology. Electrophoresis 32, 2410–2427 (2011).

    Article  CAS  PubMed  Google Scholar 

  14. Pamme, N. Continuous flow separations in microfluidic devices. Lab Chip 7, 1644–1659 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Robert, D. et al. Cell sorting by endocytotic capacity in a microfluidic magnetophoresis device. Lab Chip 11, 1902–1910 (2011).

    Article  CAS  PubMed  Google Scholar 

  16. Shen, F., Hwang, H., Hahn, Y.K. & Park, J.-K. Labelfree cell separation using a tunable magnetophoretic repulsion force. Anal. Chem. 84, 3075–3081 (2012).

    Article  CAS  PubMed  Google Scholar 

  17. Shi, J., Huang, H., Stratton, Z, Huang, Y. & Huang, T.J. Continuous particle separation in a microfluidic channel via standing surface acoustic waves (SSAW). Lab Chip 9, 3354–3359 (2009).

    Article  CAS  PubMed  Google Scholar 

  18. Li, P. et al. Acoustic separation of circulating tumor cells. Proc. Natl. Acad. Sci. U.S.A. 112, 4970–4975 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Urbansky, A. et al. Rapid and effective enrichment of mononuclear cells from blood using acoustophoresis. Sci. Rep. 7, 17161 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wang, X. et al. Enhanced cell sorting and manipulation with combined optical tweezer and microfluidic chip technologies. Lab Chip 11, 3656–3662 (2011).

    Article  CAS  PubMed  Google Scholar 

  21. Landenberger, B., Höfemann, H., Wadle, S. & Rohrbach, A. Microfluidic sorting of arbitrary cells with dynamic optical tweezers. Lab Chip 12, 3177–3183 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Yamada, M., Nakashima, M. & Seki, M. Pinched flow fractionation: Continuous size separation of particles utilizing a laminar flow profile in a pinched microchannel. Anal. Chem. 76, 5465–5471 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Ashley, J.F., Bowman, C.N. & Davis, R.H. Hydrodynamic separation of particles using pinched-flow fractionation. AIChE J. 59, 3444–3457 (2013). https://doi. org/10.1002/aic.14087

    Article  CAS  Google Scholar 

  24. Huang, L.R., Cox, E.C., Austin, R.H. & Sturm, J.C. Continuous particle separation through deterministic lateral displacement. Science 304, 987–990 (2004).

    Article  CAS  Google Scholar 

  25. McGrath, J., Jimenez, M. & Bridle, H. Deterministic lateral displacement for particle separation: a review. Lab Chip 14, 4139–4158 (2014).

    Article  CAS  PubMed  Google Scholar 

  26. Tran, T.S.H., Ho, B.D., Beech, J.P. & Tegenfeldt, J.O. Open channel deterministic lateral displacement for particle and cell sorting. Lab Chip 17, 3592–3600 (2017).

    Article  CAS  PubMed  Google Scholar 

  27. Choi, S. & Park, J.-K. Continuous hydrophoretic separation and sizing of microparticles using slanted obstacles in a microchannel. Lab Chip 7, 890–897 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Choi, S., Song, S., Choi, C. & Park, J.-K. Hydrophoretic sorting of micrometer and submicrometer particles using anisotropic microfluidic obstacles. Anal. Chem. 81, 50–55 (2009).

    Article  CAS  PubMed  Google Scholar 

  29. Kim, B., Lee, J.K. & Choi, S. Continuous sorting and washing of cancer cells from blood cells by hydrophoresis. BioChip J. 10, 81–87 (2016). https://doi. org/10.1007/s13206-016-0201-0

    Article  CAS  Google Scholar 

  30. Di Carlo, D. Inertial microfluidics. Lab Chip 9, 3038–3046 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Zhang, J. et al. Fundamentals and applications of inertial microfluidics: a review. Lab Chip 16, 10–34 (2016).

    Article  CAS  PubMed  Google Scholar 

  32. Godino, N., Jorde, F., Lawlor, D., Jaeger, M. & Duschl, C. Purification of microalgae from bacterial contamination using a disposable inertia-based microfluidic device. J. Micromech. Microeng. 25, 084002 (2015). http://dx.doi.org/10.1088/0960-1317/25/8/084002

    Article  CAS  Google Scholar 

  33. Di Carlo, D., Irimia, D., Tompkins, R.G. & Toner, M. Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc. Natl. Acad. Sci. U.S.A. 104, 18892–18897 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bhagat, A.A.S., Kuntaegowdanahalli, S.S. & Papautsky, I. Enhanced particle filtration in straight microchannels using shear-modulated inertial migration. Phys. Fluids 20, 101702 (2008). https://doi.org/10.1063/1.2998844

    Article  CAS  Google Scholar 

  35. Amini, H., Lee, W. & Di Carlo, D. Inertial microfluidic physics. Lab Chip 14, 2739–2761 (2014).

    Article  CAS  PubMed  Google Scholar 

  36. Lee, M.G., Choi, S. & Park, J.-K. Inertial separation in a contractio-expansion array microchannel. J. Chromatogr. A 1218, 4138–4143 (2011).

    Article  CAS  PubMed  Google Scholar 

  37. Choi, K. et al. Negative selection by spiral inertial microfluidics improves viral recovery and sequencing from blood. Anal. Chem. 90, 4657–4662 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Park, J.-S. & Jung, H.-I. Multiorifice flow fractionation: continuous size-based separation of microspheres using a series of contraction/expansion microchannels. Anal. Chem. 81, 8280–8288 (2009).

    Article  CAS  PubMed  Google Scholar 

  39. Segré, G. & Silberberg, A. Radial particle displacements in Poiseuille flow of suspensions. Nature 189, 209–210 (1961). https://doi.org/10.1038/189209a0

    Article  Google Scholar 

  40. Segré, G. & Silberberg, A. Behaviour of macroscopic rigid spheres in Poiseuille flow Part 2. Experimental results and interpretation. J. Fluid Mech. 14, 136–157 (1962). https://doi.org/10.1017/S0022112062001111

    Google Scholar 

  41. Mach. A.J. & Di Carlo, D. Continuous scalable blood filtration device using inertial microfluidics. Biotechnol. Bioeng. 107, 302–311 (2010).

    Article  CAS  PubMed  Google Scholar 

  42. Li, M., van Zee, M., Goda, K. & Di Carlo, D. Size-based sorting of hydrogel droplets using inertial microfluidics. Lab Chip 18, 2575–2582 (2018).

    Article  CAS  PubMed  Google Scholar 

  43. Zhou, J., Giridhar, P.V., Kasper, S. & Papautsky, I. Modulation of aspect ratio for complete separation in an inertial microfluidic channel. Lab Chip 13, 1919–1929 (2013).

    Article  CAS  PubMed  Google Scholar 

  44. Tan, A.P. et al. Continuous-flow cytomorphological staining and analysis. Lab Chip 14, 522–531 (2014).

    Article  CAS  PubMed  Google Scholar 

  45. Dudani, J.S., Go, D.E., Gossett, D.R., Tan, A.P. & Di Carlo, D. Mediating millisecond reaction time around particles and cells. Anal. Chem. 86, 1502–1510 (2014).

    Article  CAS  PubMed  Google Scholar 

  46. Dudani, J.S. et al. Rapid inertial solution exchange for enrichment and flow cytometric detection of microvesicles. Biomicrofluidics 9, 014112 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shen, S. et al. Regulating secondary flow in ultra-low aspect ratio microchannels by dimensional confinement. Adv. Theory Simul. 1, 1700034 (2018). https://doi.org/10.1002/adts.201700034

    Article  CAS  Google Scholar 

  48. Bhagat, A.A.S., Kuntaegowdanahalli, S.S., Kaval, N., Seliskar, C.J. & Papautsky, I. Inertial microfluidics for sheath-less high-throughput flow cytometry. Biomed. Microdevices 12, 187–195 (2010).

    Article  PubMed  Google Scholar 

  49. Lee, M.G. et al. Inertial blood plasma separation in a contraction-expansion array microchannel. Appl. Phys. Lett. 98, 253702 (2011). https://doi.org/10.1063/1.3601745

    Article  CAS  Google Scholar 

  50. Lee, M.G., Shin, J.H., Bae, C.Y., Choi, S. & Park, J.-K. Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress, Anal. Chem. 85, 6213–6218 (2013).

    CAS  Google Scholar 

  51. Lee, M.G., Shin, J.H., Choi, S. & Park, J.-K. Enhanced blood plasma separation by modulation of inertial lift force. Sens. Actuators B Chem. 190, 311–317 (2014). https://doi.org/10.1016/j.snb.2013.08.092

    Article  CAS  Google Scholar 

  52. Kuntaegowdanahalli, S.S., Bhagat, A.A.S., Kumar, G. & Papautsky, I. Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip 9, 2973–2980 (2009).

    Article  CAS  PubMed  Google Scholar 

  53. Zhang, J., Li, W. & Alici, G. Inertial microfluidics: mechanisms and applications. In D. Zhang & B. Wei (Eds.), Advanced Mechatronics and MEMS Devices II, 563–593 (2017).

    Chapter  Google Scholar 

  54. Hou, H.W. et al. Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci. Rep. 3, 1259 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Warkiani, M.E. et al. Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip 14, 128–137 (2014).

    Article  CAS  PubMed  Google Scholar 

  56. Lee, W. et al. 3D-printed microfluidic device for the detection of pathogenic bacteria using size-based separation in helical channel with trapezoid cross-section. Sci. Rep. 5, 7717 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Choi, J., Hong, S.C., Kim, W. & Jung, J.H. Highly enriched, controllable, continuous aerosol sampling using inertial microfluidics and its application to real-time detection of airborne bacteria. ACS Sensors 2, 513–521 (2017).

    Article  CAS  PubMed  Google Scholar 

  58. Kim, J. et al. Size-dependent inertial focusing position shift and particle separations in triangular microchannels. Anal. Chem. 90, 1827–1835 (2018).

    Article  CAS  PubMed  Google Scholar 

  59. Xu, W., Hou, Z., Liu, Z. & Wu, Z. Viscosity-differenceinduced asymmetric selective focusing for large stroke particle separation. Microfluid. Nanofluid. 20, 128 (2016).

    Article  Google Scholar 

  60. Lee, D. et al. Active control of inertial focusing positions and particle separations enabled by velocity profile tuning with coflow systems. Anal. Chem. 90, 2902–2911 (2018).

    Article  CAS  PubMed  Google Scholar 

  61. Wang, L. & Dandy, D.S. High-throughput inertial focusing of micrometer-and sub-micrometer-sized particles separation. Adv. Sci. 4, 1700153 (2017).

    Article  CAS  Google Scholar 

  62. Cruz, J. et al. High pressure inertial focusing for separating and concentrating bacteria at high throughput. J. Micromech. Microeng. 27, 084001 (2017).

    Article  CAS  Google Scholar 

  63. Mutlu, B.R., Edd, J.F. & Toner, M. Oscillatory inertial focusing in infinite microchannels. Proc. Natl. Acad. Sci. U.S.A. 115, 7682–7687 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Je-Kyun Park.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, GY., Han, JI. & Park, JK. Inertial Microfluidics-Based Cell Sorting. BioChip J 12, 257–267 (2018). https://doi.org/10.1007/s13206-018-2401-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-018-2401-2

Keywords

Navigation