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Semin Reprod Med 2011; 29(1): 005-014
DOI: 10.1055/s-0030-1268699
© Thieme Medical Publishers

Microfluidics for Gametes, Embryos, and Embryonic Stem Cells

G. D. Smith1 , 2 , 3 , 4 , J. E. Swain1 , C. L. Bormann5
  • 1Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin
  • 2Department of Molecular and Integrative Physiology, University of Wisconsin, Madison, Wisconsin
  • 3Department of Urology, University of Wisconsin, Madison, Wisconsin
  • 4Department of Reproductive Sciences Program, University of Michigan, Ann Arbor, Michigan
  • 5Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin
Further Information

Publication History

Publication Date:
04 January 2011 (online)

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ABSTRACT

Microfluidics is a young but established field that holds significant potential for scientific discovery. The utility of microfluidics can improve our knowledge of basic biology as well as expand our understanding in specialized areas such as assisted reproduction and stem cell developmental biology. This review describes the technology of microfluidics and discusses applications within assisted reproduction technology and embryonic stem cell growth and directed differentiation. Development of an integrated microfluidic platform for assisted reproduction, which can manipulate gametes, embryos, embryonic stem cells, their culture environment, and incorporate biomarker analysis, could have a dramatic impact on the basic understanding of embryo/embryonic stem cell development, as well as provide significant improvements in current technologies used to treat infertility, preserve fertility, and derive therapeutic cells from stem cells.

KEYWORDS

Sperm - blastocyst - culture - in vitro fertilization (IVF) - fertilization

REFERENCES

  • 1 Centers for Disease Control and Prevention .Assisted Reproductive Technology Success Rates; National Summary and Fertility Clinic Reports. Atlanta, GA: Centers for Disease Control and Prevention; 2001: 549
    Google Scholar
  • 2 Centers for Disease Control and Prevention .Assisted Reproductive Technology (ART) Report: National Summary. Atlanta, GA: Center for Disease Control and Prevention; 2005
    Google Scholar
  • 3 Memili E, First N L. Zygotic and embryonic gene expression in cow: a review of timing and mechanisms of early gene expression as compared with other species.  Zygote. 2000;  8 (1) 87-96
    CrossrefPubMedGoogle Scholar
  • 4 Ravindranatha B M, Nandi S, Raghu H M, Reddy S M. In vitro maturation and fertilization of buffalo oocytes: effects of storage of ovaries, IVM temperatures, storage of processed sperm and fertilization media.  Reprod Domest Anim. 2003;  38 (1) 21-26
    CrossrefPubMedGoogle Scholar
  • 5 Xie Y, Wang F, Zhong W, Puscheck E, Shen H, Rappolee D A. Shear stress induces preimplantation embryo death that is delayed by the zona pellucida and associated with stress-activated protein kinase-mediated apoptosis.  Biol Reprod. 2006;  75 (1) 45-55
    CrossrefPubMedGoogle Scholar
  • 6 Beebe D, Wheeler M, Zeringue H, Walters E, Raty S. Microfluidic technology for assisted reproduction.  Theriogenology. 2002;  57 (1) 125-135
    CrossrefPubMedGoogle Scholar
  • 7 Beebe D J, Mensing G A, Walker G M. Physics and applications of microfluidics in biology.  Annu Rev Biomed Eng. 2002;  4 261-286
    CrossrefPubMedGoogle Scholar
  • 8 Quake S R, Scherer A. From micro- to nanofabrication with soft materials.  Science. 2000;  290 (5496) 1536-1540
    CrossrefPubMedGoogle Scholar
  • 9 Sia S K, Whitesides G M. Microfluidic devices fabricated in poly(dimethylsiloxane) for biological studies.  Electrophoresis. 2003;  24 (21) 3563-3576
    CrossrefPubMedGoogle Scholar
  • 10 Walker G M, Ozers M S, Beebe D J. Insect cell culture in microfluidic channels.  Biomed Microdevices. 2002;  4 161-166
    CrossrefPubMedGoogle Scholar
  • 11 Raty S DJ, Beebe D J, Rodriguez-Zas S L, Wheeler M B. Culture in microchannels enhances in vitro embryonic development of preimplantation mouse embryos.  Theriogenology. 2001;  55 241
    PubMedGoogle Scholar
  • 12 Huang W H, Cheng W, Zhang Z et al. Transport, location, and quantal release monitoring of single cells on a microfluidic device.  Anal Chem. 2004;  76 (2) 483-488
    CrossrefPubMedGoogle Scholar
  • 13 Cho B S, Schuster T G, Zhu X, Chang D, Smith G D, Takayama S. Passively driven integrated microfluidic system for separation of motile sperm.  Anal Chem. 2003;  75 (7) 1671-1675
    CrossrefPubMedGoogle Scholar
  • 14 Davis J A, Raty S, Eddington D T et al. Development of microfluidic channels for the culture of mammalian embryos. 1st Annual International IEEE-EMBS Special Topic Conference on Microtechnologies.  Med Biol Proc. 2000;  307-310
    PubMedGoogle Scholar
  • 15 Glasgow I K, Zeringue H C, Beebe D J, Choi S J, Lyman J, Wheeler M B. Individual embryo transport on a chip for a total analysis system. Paper presented at: Third International Symposium on Micro-Total Analysis System; October 13–16, 1998; Banff, Alberta, Canada
    Google Scholar
  • 16 Schuster T G, Cho B, Keller L M, Takayama S, Smith G D. Isolation of motile spermatozoa from semen samples using microfluidics.  Reprod Biomed Online. 2003;  7 (1) 75-81
    CrossrefPubMedGoogle Scholar
  • 17 Mosher W D, Pratt W F. Fecundity and infertility in the United States: incidence and trends.  Fertil Steril. 1991;  56 (2) 192-193
    CrossrefPubMedGoogle Scholar
  • 18 Mortimer D. Sperm transfer in the human female reproductive tract. Oxford, United Kingdom: Oxford University Press; 1989
    Google Scholar
  • 19 Trounson A O, Gardner D K. Handbook of in Vitro Fertilization. Boca Raton, FL: CRC Press; 2000
    Google Scholar
  • 20 Aitken R J, Clarkson J S. Significance of reactive oxygen species and antioxidants in defining the efficacy of sperm preparation techniques.  J Androl. 1988;  9 (6) 367-376
    PubMedGoogle Scholar
  • 21 Zini A, Finelli A, Phang D, Jarvi K. Influence of semen processing technique on human sperm DNA integrity.  Urology. 2000;  56 (6) 1081-1084
    CrossrefPubMedGoogle Scholar
  • 22 Zini A, Mak V, Phang D, Jarvi K. Potential adverse effect of semen processing on human sperm deoxyribonucleic acid integrity.  Fertil Steril. 1999;  72 (3) 496-499
    CrossrefPubMedGoogle Scholar
  • 23 Virant-Klun I, Tomazevic T, Meden-Vrtovec H. Sperm single-stranded DNA, detected by acridine orange staining, reduces fertilization and quality of ICSI-derived embryos.  J Assist Reprod Genet. 2002;  19 (7) 319-328
    CrossrefPubMedGoogle Scholar
  • 24 Benchaib M, Braun V, Lornage J et al. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique.  Hum Reprod. 2003;  18 (5) 1023-1028
    CrossrefPubMedGoogle Scholar
  • 25 Seli E, Gardner D K, Schoolcraft W B, Moffatt O, Sakkas D. Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization.  Fertil Steril. 2004;  82 (2) 378-383
    CrossrefPubMedGoogle Scholar
  • 26 Bungum M, Humaidan P, Spano M, Jepson K, Bungum L, Giwercman A. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI.  Hum Reprod. 2004;  19 (6) 1401-1408
    CrossrefPubMedGoogle Scholar
  • 27 Henkel R, Hajimohammad M, Stalf T et al. Influence of deoxyribonucleic acid damage on fertilization and pregnancy.  Fertil Steril. 2004;  81 (4) 965-972
    CrossrefPubMedGoogle Scholar
  • 28 Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation.  Hum Reprod. 2004;  19 (3) 611-615
    CrossrefPubMedGoogle Scholar
  • 29 Carrell D T, Liu L, Peterson C M et al. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss.  Arch Androl. 2003;  49 (1) 49-55
    CrossrefPubMedGoogle Scholar
  • 30 Englert Y, Van den Bergh M, Rodesch C, Bertrand E, Biramane J, Legreve A. Comparative auto-controlled study between swim-up and Percoll preparation of fresh semen samples for in-vitro fertilization.  Hum Reprod. 1992;  7 (3) 399-402
    PubMedGoogle Scholar
  • 31 Smith S, Hosid S, Scott L. Use of postseparation sperm parameters to determine the method of choice for sperm preparation for assisted reproductive technology.  Fertil Steril. 1995;  63 (3) 591-597
    PubMedGoogle Scholar
  • 32 Palermo G, Joris H, Devroey P, Van Steirteghem A C. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte.  Lancet. 1992;  340 (8810) 17-18
    CrossrefPubMedGoogle Scholar
  • 33 Schultz R M, Williams C J. The science of ART.  Science. 2002;  296 (5576) 2188-2190
    CrossrefPubMedGoogle Scholar
  • 34 Palermo G D, Alikani M, Bertoli M et al. Oolemma characteristics in relation to survival and fertilization patterns of oocytes treated by intracytoplasmic sperm injection.  Hum Reprod. 1996;  11 (1) 172-176
    CrossrefPubMedGoogle Scholar
  • 35 Nagy Z P, Liu J, Joris H et al. The influence of the site of sperm deposition and mode of oolemma breakage at intracytoplasmic sperm injection on fertilization and embryo development rates.  Hum Reprod. 1995;  10 (12) 3171-3177
    PubMedGoogle Scholar
  • 36 Kricka L J, Nozaki O, Heyner S, Garside W T, Wilding P. Applications of a microfabricated device for evaluating sperm function.  Clin Chem. 1993;  39 (9) 1944-1947
    PubMedGoogle Scholar
  • 37 Kricka L J, Faro I, Heyner S et al. Micromachined analytical devices: microchips for semen testing.  J Pharm Biomed Anal. 1997;  15 (9–10) 1443-1447
    CrossrefPubMedGoogle Scholar
  • 38 Anderson J R, Chiu D T, Jackman R J et al. Fabrication of topologically complex three-dimensional microfluidic systems in PDMS by rapid prototyping.  Anal Chem. 2000;  72 (14) 3158-3164
    CrossrefPubMedGoogle Scholar
  • 39 Unger M A, Chou H P, Thorsen T, Scherer A, Quake S R. Monolithic microfabricated valves and pumps by multilayer soft lithography.  Science. 2000;  288 (5463) 113-116
    CrossrefPubMedGoogle Scholar
  • 40 Figeys D, Pinto D. Lab-on-a-chip: a revolution in biological and medical sciences.  Anal Chem. 2000;  72 (9) 330-335
    PubMedGoogle Scholar
  • 41 Dietl J A, Rauth G. Molecular aspects of mammalian fertilization.  Hum Reprod. 1989;  4 (8) 869-875
    PubMedGoogle Scholar
  • 42 Hickman D L, Beebe D J, Rodriguez-Zas S L, Wheeler M B. Comparison of static and dynamic medium environments for culturing of pre-implantation mouse embryos.  Comp Med. 2002;  52 (2) 122-126
    PubMedGoogle Scholar
  • 43 Funahashi H, Fujiwara T, Nagai T. Modulation of the function of boar spermatozoa via adenosine and fertilization promoting peptide receptors reduce the incidence of polyspermic penetration into porcine oocytes.  Biol Reprod. 2000;  63 (4) 1157-1163
    CrossrefPubMedGoogle Scholar
  • 44 Li Y H, Ma W, Li M, Hou Y, Jiao L H, Wang W H. Reduced polyspermic penetration in porcine oocytes inseminated in a new in vitro fertilization (IVF) system: straw IVF.  Biol Reprod. 2003;  69 (5) 1580-1585
    CrossrefPubMedGoogle Scholar
  • 45 Ranoux C, Poirot C, Foulot H et al. Human egg fertilization in capillary tubes.  J In Vitro Fert Embryo Transf. 1988;  5 (1) 49-50
    CrossrefPubMedGoogle Scholar
  • 46 Ranoux C, Seibel M M. New techniques in fertilization: intravaginal culture and microvolume straw.  J In Vitro Fert Embryo Transf. 1990;  7 (1) 6-8
    CrossrefPubMedGoogle Scholar
  • 47 van der Ven H H, Hoebbel K, al-Hasani S, Diedrich K, Krebs D. Fertilization of human oocytes in capillary tubes with very small numbers of spermatozoa.  Hum Reprod. 1989;  4 (1) 72-76
    PubMedGoogle Scholar
  • 48 Töpfer-Petersen E, Petrounkina A M, Ekhlasi-Hundrieser M. Oocyte-sperm interactions.  Anim Reprod Sci. 2000;  60–61 653-662
    PubMedGoogle Scholar
  • 49 Clark S G, Walters E M, Beebe D J, Wheeler M B. In vitro fertilization of porcine oocytes in polydimethylsiloxane (PDMS)-glass microchannels.  Biol Reprod. 2002;  66 528
    PubMedGoogle Scholar
  • 50 Ahlgren M. Sperm transport to and survival in the human fallopian tube.  Gynecol Invest. 1975;  6 (3–4) 206-214
    CrossrefPubMedGoogle Scholar
  • 51 Settlage D S, Motoshima M, Tredway D R. Sperm transport from the external cervical os to the fallopian tubes in women: a time and quantitation study.  Fertil Steril. 1973;  24 (9) 655-661
    PubMedGoogle Scholar
  • 52 Suh R S, Zhu X, Phadke N, Ohl D A, Takayama S, Smith G D. IVF within microfluidic channels requires lower total numbers and lower concentrations of sperm.  Hum Reprod. 2006;  21 (2) 477-483
    PubMedGoogle Scholar
  • 53 Gardner D K, Lane M. Culture of viable human blastocysts in defined sequential serum-free media.  Hum Reprod. 1998;  13 (Suppl 3) 148-159 discussion 160
    CrossrefPubMedGoogle Scholar
  • 54 Beebe D J, Mensing G A, Walker G M. Physics and applications of microfluidics in biology.  Annu Rev Biomed Eng. 2002;  4 261-286
    CrossrefPubMedGoogle Scholar
  • 55 Glasgow I K, Zeringue H C, Beebe D J et al. Handling individual mammalian embryos using microfluidics.  IEEE Trans Biomed Eng. 2001;  48 (5) 570-578
    CrossrefPubMedGoogle Scholar
  • 56 Schuck P, Millar D B, Kortt A A. Determination of binding constants by equilibrium titration with circulating sample in a surface plasmon resonance biosensor.  Anal Biochem. 1998;  265 (1) 79-91
    CrossrefPubMedGoogle Scholar
  • 57 Gu W, Zhu X, Futai N, Cho B S, Takayama S. Computerized microfluidic cell culture using elastomeric channels and Braille displays.  Proc Natl Acad Sci U S A. 2004;  101 (45) 15861-15866
    CrossrefPubMedGoogle Scholar
  • 58 Gardner D K, Vella P, Lane M, Wagley L, Schlenker T, Schoolcraft W B. Culture and transfer of human blastocysts increases implantation rates and reduces the need for multiple embryo transfers.  Fertil Steril. 1998;  69 (1) 84-88
    CrossrefPubMedGoogle Scholar
  • 59 Gerecht-Nir S, Cohen S, Itskovitz-Eldor J. Bioreactor cultivation enhances the efficiency of human embryoid body (hEB) formation and differentiation.  Biotechnol Bioeng. 2004;  86 (5) 493-502
    CrossrefPubMedGoogle Scholar
  • 60 Fong W J, Tan H L, Choo A, Oh S K. Perfusion cultures of human embryonic stem cells.  Bioprocess Biosyst Eng. 2005;  27 (6) 381-387
    CrossrefPubMedGoogle Scholar
  • 61 Kim L, Vahey M D, Lee H-Y, Voldman J. Microfluidic arrays for logarithmically perfused embryonic stem cell culture.  Lab Chip. 2006;  6 (3) 394-406
    CrossrefPubMedGoogle Scholar
  • 62 Villa-Diaz L G, Pacut C, Slawny N A, Ding J, O'Shea K S, Smith G D. Analysis of the factors that limit the ability of feeder cells to maintain the undifferentiated state of human embryonic stem cells.  Stem Cells Dev. 2009;  18 (4) 641-651
    CrossrefPubMedGoogle Scholar
  • 63 Cheng W, Klauke N, Sedgwick H, Smith G L, Cooper J M. Metabolic monitoring of the electrically stimulated single heart cell within a microfluidic platform.  Lab Chip. 2006;  6 (11) 1424-1431
    CrossrefPubMedGoogle Scholar
  • 64 Shackman J G, Dahlgren G M, Peters J L, Kennedy R T. Perfusion and chemical monitoring of living cells on a microfluidic chip.  Lab Chip. 2005;  5 (1) 56-63
    CrossrefPubMedGoogle Scholar
  • 65 Mehta G, Mehta K, Sud D et al. Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture.  Biomed Microdevices. 2007;  9 (2) 123-134
    CrossrefPubMedGoogle Scholar

Gary D Smith

Departments of Obstetrics and Gynecology, Physiology, and Urology, University of Michigan

6410 Medical Science 1, 1301 E. Catherine Street, Ann Arbor, MI 48109-0617

Email: smithgd@umich.edu

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