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High-throughput blood cell focusing and plasma isolation using spiral inertial microfluidic devices

Biomedical Microdevices volume 17, Article number: 110 (2015) Cite this article

Abstract

Herein, we explored the blood cell focusing and plasma isolation using a spiral inertial microfluidic device. First, the flow-rate and concentration effects on the migration dynamics of blood cells were systematically investigated to uncover the focusing mechanisms and steric crowding effects of cells in Dean-coupled inertial flows. A novel phenomenon that the focusing status of discoid red blood cells (RBCs) changes according to the channel height was discovered. These experimental data may provide valuable insights for the high-throughput processing of blood samples using inertial microfluidics. On the basis of the improved understandings on blood cell focusing, efficient isolation of plasma from whole blood with a 20-fold dilution was achieved at a throughput up to 700 μl/min. The purity of the isolated blood plasma was close to 100 %, and the plasma yield was calculated to be 38.5 %. As compared with previously-reported devices, our spiral inertial microfluidic device provides a balanced overall performance, and has overriding advantages in terms of processing throughput and operating efficiency.

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References

  • H. Amini, W. Lee, D. Di Carlo, Inertial microfluidic physics. Lab Chip 14(15), 2739–2761 (2014)

    Article  Google Scholar 

  • E.S. Asmolov, The inertial lift on a spherical particle in a plane Poiseuille flow at large channel Reynolds number. J. Fluid Mech. 381(-1), 63–87 (1999)

    MATH  MathSciNet  Article  Google Scholar 

  • S.A. Berger, L. Talbot, L.S. Yao, Flow in curved pipes. Annu. Rev. Fluid Mech. 15(1), 461–512 (1983)

    Article  Google Scholar 

  • A.A.S. Bhagat, S.S. Kuntaegowdanahalli, I. Papautsky, Continuous particle separation in spiral microchannels using dean flows and differential migration. Lab Chip 8(11), 1906–1914 (2008)

    Article  Google Scholar 

  • Y.-H. Chen, Z.-K. Kuo, C.-M. Cheng, Paper–a potential platform in pharmaceutical development. Trends Biotechnol. 33(1), 4–9 (2015)

    Article  Google Scholar 

  • R.G. Cox, H. Brenner, The lateral migration of solid particles in Poiseuille flow -- I theory. Chem. Eng. Sci. 23(2), 147–173 (1968)

    Article  Google Scholar 

  • C.G. Craddock, S. Perry, J.S. Lawrence, The dynamics of leukopenia and leukocytosis. Ann. Intern. Med. 52(2), 281–294 (1960)

    Article  Google Scholar 

  • W.R. Dean, Fluid motion in a curved channel. Proc. R. Soc. A 121(787), 402–420 (1928)

    MATH  Article  Google Scholar 

  • D. Di Carlo, Inertial microfluidics. Lab Chip 9(21), 3038–3046 (2009)

    Article  Google Scholar 

  • D. Di Carlo, D. Irimia, R.G. Tompkins, M. Toner, Continuous inertial focusing, ordering, and separation of particles in microchannels. Proc. Natl. Acad. Sci. U. S. A. 104(48), 18892–18897 (2007)

    Article  Google Scholar 

  • D.R. Gossett, D. Di Carlo, Particle focusing mechanisms in curving confined flows. Anal. Chem. 81(20), 8459–8465 (2009)

    Article  Google Scholar 

  • S. Haeberle, T. Brenner, R. Zengerle, J. Ducree, Centrifugal extraction of plasma from whole blood on a rotating disk. Lab Chip 6(6), 776–781 (2006)

    Article  Google Scholar 

  • J. Hai, W. Xuan, C. Chan Hee, W. Xudong, L. Dongqing, A microfluidic chip for blood plasma separation using electro-osmotic flow control. J. Micromech. Microeng. 21(8), 085019 (2011)

    Article  Google Scholar 

  • D. Heikali, D. Di Carlo, A niche for microfluidics in portable hematology analyzers. JALA 15(4), 319–328 (2010)

    Google Scholar 

  • B.P. Ho, L.G. Leal, Inertial migration of rigid spheres in two-dimensional unidirectional flows. J. Fluid Mech. 65(02), 365–400 (1974)

    MATH  Article  Google Scholar 

  • H.W. Hou, M.E. Warkiani, B.L. Khoo, Z.R. Li, R.A. Soo, D.S.-W. Tan, W.-T. Lim, J. Han, A.A.S. Bhagat, C.T. Lim, Isolation and retrieval of circulating tumor cells using centrifugal forces. Sci. Rep. 3, 1259 (2013)

    Google Scholar 

  • H.W. Hou, R.P. Bhattacharyya, D.T. Hung, J. Han, Direct detection and drug-resistance profiling of bacteremias using inertial microfluidics. Lab Chip 15(10), 2297–2307 (2015)

    Article  Google Scholar 

  • S.C. Hur, H.T.K. Tse, D. Di Carlo, Sheathless inertial cell ordering for extreme throughput flow cytometry. Lab Chip 10(3), 274–280 (2010)

    Article  Google Scholar 

  • N.M. Karabacak, P.S. Spuhler, F. Fachin, E.J. Lim, V. Pai, E. Ozkumur, J.M. Martel, N. Kojic, K. Smith, C. P-i, J. Yang, H. Hwang, B. Morgan, J. Trautwein, T.A. Barber, S.L. Stott, S. Maheswaran, R. Kapur, D.A. Haber, M. Toner, Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat. Protoc. 9(3), 694–710 (2014)

    Article  Google Scholar 

  • M. Kersaudy-Kerhoas, E. Sollier, Micro-scale blood plasma separation: from acoustophoresis to egg-beaters. Lab Chip 13(17), 3323–3346 (2013)

    Article  Google Scholar 

  • S.S. Kuntaegowdanahalli, A.A.S. Bhagat, G. Kumar, I. Papautsky, Inertial microfluidics for continuous particle separation in spiral microchannels. Lab Chip 9(20), 2973–2980 (2009)

    Article  Google Scholar 

  • M.G. Lee, J.H. Shin, C.Y. Bae, S. Choi, J.-K. Park, Label-free cancer cell separation from human whole blood using inertial microfluidics at low shear stress. Anal. Chem. 85(13), 6213–6218 (2013)

    Article  Google Scholar 

  • M.G. Lee, J.H. Shin, S. Choi, J.-K. Park, Enhanced blood plasma separation by modulation of inertial lift force. Sensors Actuators B 190, 311–317 (2014)

    Article  Google Scholar 

  • A. Lenshof, A. Ahmad-Tajudin, K. Järås, A.-M. Swärd-Nilsson, L. Åberg, G. Marko-Varga, J. Malm, H. Lilja, T. Laurell, Acoustic whole blood plasmapheresis chip for prostate specific antigen microarray diagnostics. Anal. Chem. 81(15), 6030–6037 (2009)

    Article  Google Scholar 

  • C. Liu, G. Hu, X. Jiang, J. Sun, Inertial focusing of spherical particles in rectangular microchannels over a wide range of Reynolds numbers. Lab Chip 15(4), 1168–1177 (2015)

    Article  Google Scholar 

  • M. Lokhandwalla, J.A. McAteer, J.C. Williams Jr., B. Sturtevant, Mechanical haemolysis in shock wave lithotripsy (SWL): II. In vitro cell lysis due to shear. Phys. Med. Biol. 46(4), 1245 (2001)

    Article  Google Scholar 

  • A.J. Mach, D. Di Carlo, Continuous scalable blood filtration device using inertial microfluidics. Biotechnol. Bioeng. 107(2), 302–311 (2010)

    Article  Google Scholar 

  • A.J. Mach, O.B. Adeyiga, D. Di Carlo, Microfluidic sample preparation for diagnostic cytopathology. Lab Chip 13(6), 1011–1026 (2013)

    Article  Google Scholar 

  • J.M. Martel, M. Toner, Inertial focusing dynamics in spiral microchannels. Phys. Fluids 24(3), 032001 (2012)

    Article  Google Scholar 

  • J.M. Martel, M. Toner, Inertial focusing in microfluidics. Annu. Rev. Biomed. Eng. 16(1), 371–396 (2014)

    Article  Google Scholar 

  • J.-P. Matas, J.F. Morris, E. Guazzelli, Inertial migration of rigid spherical particles in Poiseuille flow. J. Fluid Mech. 515(-1), 171–195 (2004)

    MATH  Article  Google Scholar 

  • K. Miura, T. Itano, M. Sugihara-Seki, Inertial migration of neutrally buoyant spheres in a pressure-driven flow through square channels. J. Fluid Mech. 749, 320–330 (2014)

    Article  Google Scholar 

  • M. Mohammadi, H. Madadi, J. Casals-Terré, J. Sellarès, Hydrodynamic and direct-current insulator-based dielectrophoresis (H-DC-iDEP) microfluidic blood plasma separation. Anal. Bioanal. Chem. 407(16), 4733–4744 (2015)

    Article  Google Scholar 

  • A. Nilghaz, W. Shen, Low-cost blood plasma separation method using salt functionalized paper. RSC Adv. 5(66), 53172–53179 (2015)

    Article  Google Scholar 

  • N. Nivedita, I. Papautsky, Continuous separation of blood cells in spiral microfluidic devices. Biomicrofluidics 7(5), 054101 (2013)

    Article  Google Scholar 

  • A. Russom, A.K. Gupta, S. Nagrath, D. Di Carlo, J.F. Edd, M. Toner, Differential inertial focusing of particles in curved low-aspect-ratio microchannels. New J. Phys. 11(7), 75025 (2009)

    Article  Google Scholar 

  • P.G. Saffman, The lift on a small sphere in a slow shear flow. J. Fluid Mech. 22(02), 385–400 (1965)

    MATH  Article  Google Scholar 

  • J.A. Schonberg, E.J. Hinch, Inertial migration of a sphere in Poiseuille flow. J. Fluid Mech. 203, 517–524 (1989)

    MATH  MathSciNet  Article  Google Scholar 

  • G. Segre, A. Silberberg, Radial particle displacements in Poiseuille flow of suspensions. Nature 189(4760), 209–210 (1961)

    Article  Google Scholar 

  • E. Sollier, C. Murray, P. Maoddi, D. Di Carlo, Rapid prototyping polymers for microfluidic devices and high pressure injections. Lab Chip 11(22), 3752–3765 (2011)

    Article  Google Scholar 

  • T.M. Squires, S.R. Quake, Microfluidics: fluid physics at the nanoliter scale. Rev. Mod. Phys. 77(3), 977–1026 (2005)

    Article  Google Scholar 

  • M.J. Stuart, R.L. Nagel, Sickle-cell disease. Lancet 364(9442), 1343–1360 (2004)

    Article  Google Scholar 

  • A.P. Sudarsan, V.M. Ugaz, Fluid mixing in planar spiral microchannels. Lab Chip 6(1), 74–82 (2006)

    Article  Google Scholar 

  • J. Sun, M. Li, C. Liu, Y. Zhang, D. Liu, W. Liu, G. Hu, X. Jiang, Double spiral microchannel for label-free tumor cell separation and enrichment. Lab Chip 12(20), 3952–3960 (2012)

    Article  Google Scholar 

  • M. Toner, D. Irimia, Blood-on-a-chip. Annu. Rev. Biomed. Eng. 7, 77–103 (2005)

    Article  Google Scholar 

  • S. Tripathi, Y.B.V. Kumar, A. Prabhakar, S.S. Joshi, A. Agrawal, Passive blood plasma separation at the microscale: a review of design principles and microdevices. J. Micromech. Microeng. 25(8), 083001 (2015)

    Article  Google Scholar 

  • M.E. Warkiani, G. Guan, K.B. Luan, W.C. Lee, A.A.S. Bhagat, P.K. Chaudhuri, D.S.-W. Tan, W.T. Lim, S.C. Lee, P.C. Chen, Slanted spiral microfluidics for the ultra-fast, label-free isolation of circulating tumor cells. Lab Chip 14(1), 128–137 (2014)

    Article  Google Scholar 

  • H. Wei Hou, H.Y. Gan, A.A.S. Bhagat, L.D. Li, C.T. Lim, J. Han, A microfluidics approach towards high-throughput pathogen removal from blood using margination. Biomicrofluidics 6(2), 024115 (2012)

    Article  Google Scholar 

  • G.M. Whitesides, E. Ostuni, S. Takayama, X. Jiang, D.E. Ingber, Soft lithography in biology and biochemistry. Annu. Rev. Biomed. Eng. 3(1), 335–373 (2001)

    Article  Google Scholar 

  • L. Wu, G. Guan, H.W. Hou, A.A.S. Bhagat, J. Han, Separation of leukocytes from blood using spiral channel with trapezoid cross-section. Anal. Chem. 84(21), 9324–9331 (2012)

    Article  Google Scholar 

  • N. Xiang, H. Yi, K. Chen, D. Sun, D. Jiang, Q. Dai, Z. Ni, High-throughput inertial particle focusing in a curved microchannel: insights into the flow-rate regulation mechanism and process model. Biomicrofluidics 7, 044116 (2013)

    Article  Google Scholar 

  • X. Xuan, J. Zhu, C. Church, Particle focusing in microfluidic devices. Microfluid. Nanofluid. 9(1), 1–16 (2010)

    Article  Google Scholar 

  • S. Yan, J. Zhang, G. Alici, H. Du, Y. Zhu, W. Li, Isolating plasma from blood using a dielectrophoresis-active hydrophoretic device. Lab Chip 14(16), 2993–3003 (2014)

    Article  Google Scholar 

  • Z.T.F. Yu, K.M. Aw Yong, J. Fu, Microfluidic blood cell sorting: now and beyond. Small 10(9), 1687–1703 (2014)

    Article  Google Scholar 

  • J. Zhang, S. Yan, R. Sluyter, W. Li, G. Alici, N.-T. Nguyen, Inertial particle separation by differential equilibrium positions in a symmetrical serpentine micro-channel. Sci. Rep. 4, 4527 (2014)

    Google Scholar 

  • J. Zhou, I. Papautsky, Fundamentals of inertial focusing in microchannels. Lab Chip 13(6), 1121–1132 (2013)

    Article  Google Scholar 

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Acknowledgments

This research work was supported by the National Natural Science Foundation of China (51505082, 51375089), the Natural Science Foundation of Jiangsu Province (BK20150606), and the “333” Project of Jiangsu Province (BRA2015291). We thank Baifeng Qian and Lu Chen from Zhongda Hospital for providing us with the blood samples.

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  1. School of Mechanical Engineering, and Jiangsu Key Laboratory for Design and Manufacture of Micro-Nano Biomedical Instruments, Southeast University, Nanjing, 211189, China

    Nan Xiang & Zhonghua Ni

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  1. Nan Xiang
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  2. Zhonghua Ni
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Correspondence to Nan Xiang.

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Xiang, N., Ni, Z. High-throughput blood cell focusing and plasma isolation using spiral inertial microfluidic devices. Biomed Microdevices 17, 110 (2015). https://doi.org/10.1007/s10544-015-0018-y

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  • DOI: https://doi.org/10.1007/s10544-015-0018-y

Keywords

  • Blood cell focusing
  • Plasma isolation
  • Inertial microfluidics
  • High-throughput processing
  • Migration dynamics