Skip to main content
Log in

Sorting spermatozoa by morphology using magnetophoresis

Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

The chances of successful fertilisation, be it in natural pregnancy, or in vivo and in vitro assisted reproduction, are significantly dependent on the percentage of morphologically normal spermatozoa. Here, we propose sorting spermatozoa by magnetophoresis and shear flow to reduce the percentage of abnormal sperm cells for assisted reproduction. By applying resistive force theory, we develop a theoretical model to compute the swimming velocity as a function of the sperm physical parameters, as well as magnetic field properties. As spermatozoa parameters vary, we implement a statistical approach and run a Monte Carlo simulation to obtain the swimming velocity displayed in box-and-whisker plots. The difference between the velocity of conditionally satisfactory spermatozoa and morphologically abnormal spermatozoa can be enlarged through various combinations of magnetophoresis and shear flow. There exists a clear trend that by using a greater magnetic force or flow rate in the direction against the sperm heading, the percentage of conditionally satisfactory sperm obtainable can be increased, although at the expense of a lower yield. It has been demonstrated that spermatozoa subjected to magnetic fields exhibit uncompromised fertilisation capability. Therefore, sorting by magnetophoresis has the potential to increase the chances of conception in assisted reproduction technology.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

References

  • Bartoov B, Eltes F, Pansky M, Langzam J, Reichart M, Soffer Y (1994) Andrology: improved diagnosis of male fertility potential via a combination of quantitative ultramorphology and routine semen analyses. Hum Reprod 9:2069–2075

    Article  Google Scholar 

  • Bartoov B, Berkovitz A, Eltes F, Kogosowski A, Menezo Y, Barak Y (2002) Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. J Androl 23:1–8

    Article  Google Scholar 

  • Bayly PV, Lewis BL, Ranz EC, Okamoto RJ, Pless RB, Dutcher SK (2011) Propulsive forces on the flagellum during locomotion of Chlamydomonas reinhardtii. Biophys J 100:2716–2725

    Article  Google Scholar 

  • Ben-David Makhluf S, Qasem R, Rubinstein S, Gedanken A, Breitbart H (2006) Loading magnetic nanoparticles into sperm cells does not affect their functionality. Langmuir 22:9480–9482

    Article  Google Scholar 

  • Berkovitz A, Eltes F, Soffer Y, Zabludovsky N, Beyth Y, Farhi J, Levran D, Bartoov B (1999) ART success and in vivo sperm cell selection depend on the ultramorphological status of spermatozoa. Andrologia 31:1–8

    Article  Google Scholar 

  • Bretherton FP, Rothschild (1961) Rheotaxis of spermatozoa. Proc R Soc Ser B 153:490–502

    Article  Google Scholar 

  • Chen YA, Huang ZW, Tsai FS, Chen CY, Lin CM, Wo AM (2011) Analysis of sperm concentration and motility in a microfluidic device. Microfluid Nanofluid 10:59–67

    Article  Google Scholar 

  • Cui KH (1997) Size differences between human X and Y spermatozoa and prefertilization diagnosis. Mol Hum Reprod 3:61–67

    Article  Google Scholar 

  • Cui W (2010) Mother or nothing: the agony of infertility. Bull World Health Organ 88:881–882

    Article  Google Scholar 

  • David G, Serres C, Jouannet P (1981) Kinematics of human spermatozoa. Gamete Res 4:83–95

    Article  Google Scholar 

  • De Mestre NJ, Russel WB (1975) Low-Reynolds-number translation of a slender cylinder near a plane wall. J Eng Math 9:81–91

    Article  MATH  Google Scholar 

  • De Vos A, Van De Velde H, Joris H, Verheyen G, Devroey P, Van Steirteghem A (2003) Influence of individual sperm morphology on fertilization, embryo morphology, and pregnancy outcome of intracytoplasmic sperm injection. Fertil Steril 79:42–48

    Article  Google Scholar 

  • Denissenko P, Kantsler V, Smith DJ, Kirkman-Brown J (2012) Human spermatozoa migration in microchannels reveals boundary-following navigation. Proc Natl Acad Sci 109:8007–8010

    Article  Google Scholar 

  • Drescher K, Dunkel J, Cisneros LH, Ganguly S, Goldstein RE (2011) Fluid dynamics and noise in bacterial cell–cell and cell–surface scattering. Proc Natl Acad Sci 108:10940–10945

    Article  Google Scholar 

  • Eggert-Kruse W, Schwarz H, Rohr G, Demirakca T, Tilgen W, Runnebaum B (1996) Sperm morphology assessment using strict criteria and male fertility under in vivo conditions of conception. Hum Reprod 11:139–146

    Article  Google Scholar 

  • Gillies EA, Cannon RM, Green RB, Pacey AA (2009) Hydrodynamic propulsion of human sperm. J Fluid Mech 625:445–474

    Article  MathSciNet  MATH  Google Scholar 

  • Gray J, Hancock JG (1955) The propulsion of sea-urchin spermatozoa. J Exp Biol 32:802–814

    Google Scholar 

  • Grow DR, Oehninger S, Seltman HJ, Toner JP, Swanson RJ, Kruger TF, Muasher SJ (1994) Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population. Fertil Steril 62:559–567

    Article  Google Scholar 

  • Happel J, Brenner H (2012) Low Reynolds number hydrodynamics: with special applications to particulate media, vol 1. Springer Science & Business Media, Berlin

    MATH  Google Scholar 

  • Hejazian M, Li W, Nguyen NT (2015) Lab on a chip for continuous-flow magnetic cell separation. Lab Chip 15:959–970

    Article  Google Scholar 

  • Human Fertilisation Embryology Authority, United Kingdom. http://www.hfea.gov.uk/fertility-treatments.html. Accessed 06 Feb 2017

  • Jeffery GB (1922) The motion of ellipsoidal particles immersed in a viscous fluid. Proc R Soc Lond Ser A 102:161–179

    Article  MATH  Google Scholar 

  • Johnson LA, Flook JP, Hawk HW (1989) Sex preselection in rabbits: live births from X and Y sperm separated by DNA and cell sorting. Biol Reprod 41:199–203

    Article  Google Scholar 

  • Kantsler V, Dunkel J, Blayney M, Goldstein RE (2014) Rheotaxis facilitates upstream navigation of mammalian sperm cells. Elife 3:e02403

    Google Scholar 

  • Katz DF, Diel L, Overstreet JW (1982) Differences in the movement of morphologically normal and abnormal human seminal spermatozoa. Biol Reprod 26:566–570

    Article  Google Scholar 

  • Keaveny EE, Maxey MR (2008) Interactions between comoving magnetic microswimmers. Phys Rev E 77:041910

    Article  Google Scholar 

  • Kim M, Powers TR (2005) Deformation of a helical filament by flow and electric or magnetic fields. Phys Rev E 71:021914

    Article  Google Scholar 

  • Kirkman-Brown JC, Smith DJ (2011) Sperm motility: is viscosity fundamental to progress? Mol Hum Reprod 17:539–544

    Article  Google Scholar 

  • Koh JBY, Marcos (2014) Effect of dielectrophoresis on spermatozoa. Microfluid Nanofluid 17:613–622

    Article  Google Scholar 

  • Koh JBY, Marcos (2015a) The study of spermatozoa and sorting in relation to human reproduction. Microfluid Nanofluid 18:755–774

    Article  Google Scholar 

  • Koh JBY, Marcos (2015b) Dielectrophoresis of spermatozoa in viscoelastic medium. Electrophoresis 36:1514–1521

    Article  Google Scholar 

  • Koh JBY, Shen X, Marcos (2016) Theoretical modeling in microscale locomotion. Microfluid Nanofluid 20:1–27

    Article  Google Scholar 

  • Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Veeck LL, Morshedi M, Brugo S (1987) New method of evaluating sperm morphology with predictive value for human in vitro fertilization. Urology 30:248–251

    Article  Google Scholar 

  • Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S (1988) Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril 49:112–117

    Article  Google Scholar 

  • Lai D, Takayama S, Smith GD (2015) Recent microfluidic devices for studying gamete and embryo biomechanics. J Biomech 48:1671–1678

    Article  Google Scholar 

  • Lam RH, Cui X, Guo W, Thorsen T (2016) High-throughput dental biofilm growth analysis for multiparametric microenvironmental biochemical conditions using microfluidics. Lab Chip 16:1652–1662

    Article  Google Scholar 

  • Lewpiriyawong N, Kandaswamy K, Yang C, Ivanov V, Stocker R (2011) Microfluidic characterization and continuous separation of cells and particles using conducting poly (dimethyl siloxane) electrode induced alternating current-dielectrophoresis. Anal Chem 83:9579–9585

    Article  Google Scholar 

  • Lighthill J (1976) Flagellar hydrodynamics. SIAM Rev 18:161–230

    Article  MathSciNet  MATH  Google Scholar 

  • Marcos, Ooi KT, Yang C, Chai JC, Wong TN (2005) Developing electro-osmotic flow in closed-end micro-channels. Int J Eng Sci 43:1349–1362

    Article  Google Scholar 

  • Marcos, Fu HC, Powers TR, Stocker R (2009) Separation of microscale chiral objects by shear flow. Phys Rev Lett 102:158103

    Article  Google Scholar 

  • Marcos FuHC, Powers TR, Stocker R (2012) Bacterial rheotaxis. Proc Natl Acad Sci 109:4780–4785

    Article  Google Scholar 

  • Marcos, Tran NP, Saini AR, Ong KCH, Chia WJ (2014) Analysis of a swimming sperm in a shear flow. Microfluid Nanofluid 17:809–819

    Article  Google Scholar 

  • Menkveld R (2013) Sperm morphology assessment using strict (tygerberg) criteria. Spermatogenesis Methods Protoc 927:39–50

    Article  Google Scholar 

  • Menkveld R, Kruger TF (1995) Advantages of strict (Tygerberg) criteria for evaluation of sperm morphology. Int J Androl 18:36–42

    Google Scholar 

  • Menkveld R, Stander FS, Kruger TF, van Zyl JA (1990) The evaluation of morphological characteristics of human spermatozoa according to stricter criteria. Hum Reprod 5:586–592

    Article  Google Scholar 

  • Menkveld R, Wong WY, Lombard CJ, Wetzels AM, Thomas CM, Merkus HM, Steegers-Theunissen RP (2001) Semen parameters, including WHO and strict criteria morphology, in a fertile and subfertile population: an effort towards standardization of in vivo thresholds. Hum Reprod 16:1165–1171

    Article  Google Scholar 

  • Miki K, Clapham DE (2013) Rheotaxis guides mammalian sperm. Curr Biol 23:443–452

    Article  Google Scholar 

  • Moore LR, Rodriguez AR, Williams PS, McCloskey K, Bolwell BJ, Nakamura M, Chalmers JJ, Zborowski M (2001) Progenitor cell isolation with a high-capacity quadrupole magnetic flow sorter. J Magn Magn Mater 225:277–284

    Article  Google Scholar 

  • Munné S (1994) Flow cytometry separation of X and Y spermatozoa could be detrimental for human embryos. Hum Reprod 9:758

    Article  Google Scholar 

  • Ombelet W, Deblaere K, Bosmans E, Cox A, Jacobs P, Janssen M, Nijs M (2003) Semen quality and intrauterine insemination. Reprod BioMed Online 7:485–492

    Article  Google Scholar 

  • Paasch U, Grunewald S, Fitzl G, Glander HJ (2003) Deterioration of plasma membrane is associated with activated caspases in human spermatozoa. J Androl 24:246–252

    Article  Google Scholar 

  • Pedley TJ, Kessler JO (1992) Hydrodynamic phenomena in suspensions of swimming microorganisms. Annu Rev Fluid Mech 24:313–358

    Article  MathSciNet  MATH  Google Scholar 

  • Pethig R (2010) Dielectrophoresis: status of the theory, technology, and applications. Biomicrofluidics 4:022811

    Article  Google Scholar 

  • Peyman SA, Kwan EY, Margarson O, Iles A, Pamme N (2009) Diamagnetic repulsion—a versatile tool for label-free particle handling in microfluidic devices. J Chromatogr A 1216:9055–9062

    Article  Google Scholar 

  • Rawe VY, Boudri HU, Sedó CA, Carro M, Papier S, Nodar F (2010) Healthy baby born after reduction of sperm DNA fragmentation using cell sorting before ICSI. Reprod BioMed Online 20:320–323

    Article  Google Scholar 

  • Roberts AM (1970) Motion of spermatozoa in fluid streams. Nature 228:375–376

    Article  Google Scholar 

  • Said TM, Grunewald S, Paasch U, Glander HJ, Baumann T, Kriegel C, Li L, Agarwal A (2005) Advantage of combining magnetic cell separation with sperm preparation techniques. Reprod BioMed Online 10:740–746

    Article  Google Scholar 

  • Said TM, Agarwal A, Zborowski M, Grunewald S, Glander HJ, Paasch U (2008) Andrology Lab Corner: utility of magnetic cell separation as a molecular sperm preparation technique. J Androl 29:134–142

    Article  Google Scholar 

  • Schulze K, Koch A, Schöpf B, Petri A, Steitz B, Chastellain M, Hofmann M, Hofmann H, von Rechenberg B (2005) Intraarticular application of superparamagnetic nanoparticles and their uptake by synovial membrane—an experimental study in sheep. J Magn Magn Mater 293:419–432

    Article  Google Scholar 

  • Schuster TG, Cho B, Keller LM, Takayama S, Smith GD (2003) Isolation of motile spermatozoa from semen samples using microfluidics. Reprod BioMed Online 7:75–81

    Article  Google Scholar 

  • Senftle FE, Hambright WP (1969) Magnetic susceptibility of biological materials. In: Barnothy MF (ed) Biological effects of magnetic fields. Springer US

  • Sharpe JC, Evans KM (2009) Advances in flow cytometry for sperm sexing. Theriogenology 71:4–10

    Article  Google Scholar 

  • Singleton J, Mielke CH, Migliori A, Boebinger GS, Lacerda AH (2004) The national high magnetic field laboratory pulsed-field facility at Los Alamos National Laboratory. Phys B 346:614–617

    Article  Google Scholar 

  • Smith DJ, Gaffney EA, Blake JR, Kirkman-Brown JC (2009) Human sperm accumulation near surfaces: a simulation study. J Fluid Mech 621:289–320

    Article  MATH  Google Scholar 

  • Su TW, Xue L, Ozcan A (2012) High-throughput lensfree 3D tracking of human sperms reveals rare statistics of helical trajectories. Proc Natl Acad Sci 109:16018–16022

    Article  Google Scholar 

  • Suh TK, Schenk JL, Seidel GE (2005) High pressure flow cytometric sorting damages sperm. Theriogenology 64:1035–1048

    Article  Google Scholar 

  • Sutcliffe AG, Ludwig M (2007) Outcome of assisted reproduction. Lancet 370:351–359

    Article  Google Scholar 

  • Takano Y, Goto T (2003) Numerical analysis of small deformation of flexible helical flagellum of swimming bacteria. JSME Int J Ser C Mech Syst 46:1234–1240

    Article  Google Scholar 

  • Watarai H, Namba M (2002) Capillary magnetophoresis of human blood cells and their magnetophoretic trapping in a flow system. J Chromatogr A 961:3–8

    Article  Google Scholar 

  • Woolley DM, Crockett RF, Groom WD, Revell SG (2009) A study of synchronisation between the flagella of bull spermatozoa, with related observations. J Exp Biol 212:2215–2223

    Article  Google Scholar 

  • World Health Organisation (1992) WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge University Press, Cambridge

    Google Scholar 

  • World Health Organization (2002) Current practices and controversies in assisted reproduction

  • Xuan X (2008) Ion separation in nanofluidics. Electrophoresis 29:3737–3743

    Article  Google Scholar 

  • Zayed F, Lenton EA, Cooke ID (1997) Comparison between stimulated in vitro fertilization and stimulated intrauterine insemination for the treatment of unexplained and mild male factor infertility. Hum Reprod 12:2408–2413

    Article  Google Scholar 

Download references

Acknowledgements

Koh is grateful to Nanyang Technological University for providing him with a PhD scholarship to pursue his current research. We thank Kong TF for his comments on our manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marcos.

Ethics declarations

Conflict of interest

We declare we have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Koh, J.B.Y., Marcos Sorting spermatozoa by morphology using magnetophoresis. Microfluid Nanofluid 21, 75 (2017). https://doi.org/10.1007/s10404-017-1911-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s10404-017-1911-x

Keywords

Navigation