Skip to main content

Advertisement

SpringerLink
Log in

Paper-based diagnostic devices for evaluating the quality of human sperm

  • Research Paper
  • Published:
Microfluidics and Nanofluidics Aims and scope Submit manuscript

Abstract

Male infertility, which amounts to half of all infertility cases, is a serious problem worldwide. The percentage of fertility-related patients in sub-Saharan African countries is higher than that for the developed countries. In low-resource countries, examination of sperm characteristics for male infertility cannot be undertaken because of poor clinical access. To evaluate male fertility in assisted reproductive medicine laboratories, the numbers of motile human sperm, the degree of sperm motility, and sperm morphology have been commonly analyzed using a microscope. It is challenging to monitor the health status of human sperm in resource-limited or remote settings for two primary reasons: (1) high capital cost (equipment for currently accepted procedural standard), and (2) complexity of the currently accepted procedural standard used to simultaneously measure human sperm concentration and motility by skillful embryologists. Determining the health status of human sperm in order to evaluate fertilization capacity using various types of low-cost, easy-to-use, and rapid devices (or systems) is a longstanding but interesting biotechnologically relevant issue in various scientific communities such as male reproduction. Furthering such efforts will inherently influence birth rate in both developed and developing nations. We have demonstrated an inexpensive but robust and easy-to-handle device for monitoring the health status of human sperm made by patterning a piece of paper and measuring the activity of a specific enzyme—a simple and elegant solution. After applying semen to the hydrophilic center circle of our patterned paper, a thiazine assay can be used to suggest sperm concentration in semen, and a tetrazolium-based colorimetric assay (MTT assay) data can be used to help estimate the percentage of motile human sperm (sperm motility) in semen based on the character that motile human sperm moved in and on the paper. Using this paper-based device, we can evaluate fertility levels without consulting doctors and use our assay to compare results with World Health Organization (WHO) reference values for sperm concentration (>2×107) and motility (>50 %). The duration and cost of one entire test are 30 min and 0.1 USD, respectively. We believe that this paper-based assay system would be useful for fertility checks based on WHO references, without need of a microscope, at home. Using this assay method, males in developed or developing countries who are reluctant or unable to consult assisted reproductive technologies clinics can self-analyze their sperm characteristics. We further note that our approach adheres to WHO regulations, especially in regard to in vitro diagnostic device performance with an associated diagnostic algorithm to enhance diagnostic accuracy (compared with just one diagnostic output), and we wish to emphasize that our research could significantly advance a broad range of diagnostic developments including paper-based diagnostic devices, in vitro diagnostic devices, and diagnosis of other diseases in various divisions of translational medicine. These results, we believe, will be of interest to a wide scientific audience working in materials science (biomaterials), chemistry (analytical and clinical), lab-on-a-chip technologies (the development of diagnostic tools), reproductive medicine, bioengineering, and translational medicine.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  • Alvarez NC (2006) Infertility: the magnitude of this problem. Rev Enferm 29:59–62

    Google Scholar 

  • Bhattacharya S (2007) Infertility. In: Edmonds DK (ed) Dewhurst’s textbook of obstetrics and gynaecology, 7th edn. Blackwell, Hoboken, pp 440–460

    Chapter  Google Scholar 

  • Björndahl L, Kirkman-Brown J, Hart G, Rattle S, Barratt CLR (2006) Development of a novel home sperm test. Hum Reprod 21:145–149

    Article  Google Scholar 

  • Chen Y-A, Huang Z-W, Tsai F-S, Chen C-Y, Lin C-M, Wo AM (2011) Analysis of sperm concentration and motility in a microfluidic device. Microfluid Nanofluid 10:59–67

    Article  Google Scholar 

  • Cheng C-M, Martinez AW, Gong J, Mace CR, Phillips ST, Carrilho E, Mirica KA, Whitesides GM (2010) Paper-based ELISA. Angew Chem Int Ed 49:4771–4774

    Article  Google Scholar 

  • Cho BS, Schuster TG, Zhu X, Chang D, Smith GD, Takayama S (2003) Passively driven integrated microfluidic system for separation of motile sperm. Anal Chem 75:1671–1675

    Article  Google Scholar 

  • Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HWG, Behre HM, Haugen TB, Kruger T, Wang C, Mbizvo MT, Vogelsong KM (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16:231–245

    Article  Google Scholar 

  • Coppola MA, Klotz KL, Kim K, Cho HY, Kang J, Shetty J, Howards SS, Flickinger CJ, Herr JC (2010) SpermCheck® Fertility, an immunodiagnostic home test that detects normozoospermia and severe oligozoospermia. Hum Reprod 25:853–861

    Article  Google Scholar 

  • Dietrich GJ, Szpyrka A, Wojtczak M, Dobosz S, Goryczko K, Żakowski Ł, Ciereszko A (2005) Effects of UV irradiation and hydrogen peroxide on DNA fragmentation, motility and fertilizing ability of rainbow trout (Oncorhynchus mykiss) spermatozoa. Theriogenology 64:1809–1822

    Article  Google Scholar 

  • Gerrits T, Shaw M (2010) Biomedical infertility care in sub-Saharan Africa: a social science review of current practices, experiences and viewpoints. Facts Views Vis ObGYn 2:194–207

    Google Scholar 

  • Hammarberg K, Baker HWG, Fisher JRW (2010) Men’s experiences of infertility and infertility treatment 5 years after diagnosis of male factor infertility: a retrospective cohort study. Hum Reprod 25:2815–2820

    Article  Google Scholar 

  • Idrisa A (2005) Infertility. In: Kwawukume EY, Emuveyan EE (eds) Comprehensive gynaecology in the tropics. Graphic Packaging, Accra, pp 333–343

    Google Scholar 

  • Inhorn MC (2009) Right to assisted reproductive technology: overcoming infertility in low-resource countries. Int J Gynecol Obstet 106:172–174

    Article  Google Scholar 

  • Inhorn MC, Van Balen F (2003) Infertility around the globe:new thinking on childlessness, gender, and reproductive technologies. University of California Press, Berkeley

    Google Scholar 

  • Kfm A, Titu M, Ham NA, Raiq R, Aminul I, Ashfaque AS (2012) Male infertility—a review. J Med 13:190–199

    Google Scholar 

  • Klotz KL, Coppola MA, Labrecque M, Brugh VM III, Ramsey K, Kim K, Conaway MR, Howards SS, Flickinger CJ, Herr JC (2008) Clinical and consumer trial performance of a sensitive immunodiagnostic home test that qualitatively detects low concentrations of sperm following vasectomy. J Urol 180:2569–2576

    Article  Google Scholar 

  • Kumar A, Ghadir S, Eskondari N, Decherney AH (2007) Reproductive endocrinology and infertility. In: Decherney AH, Nathan L, Goodwin TM, Laufer N (eds) Current diagnosis and treatment in obstetrics and gynaecology, 10th edn. McGraw Hill Medical Publishing Division, New York, pp 917–925

    Google Scholar 

  • Lo S-J, Yang S-C, Yao D-J, Chen J-H, Tu W-C, Cheng C-M (2013) Molecular-level dengue fever diagnostic devices made out of paper. Lab Chip 13:2686–2692

    Article  Google Scholar 

  • Martinez AW, Phillips ST, Carrilho E, Thomas SW III, Sindi H, Whitesides GM (2008) Simple telemedicine for developing regions: camera phones and paper-based microfluidic devices for real-time, off-site diagnosis. Anal Chem 80:3699–3707

    Article  Google Scholar 

  • Martinez AW, Phillips ST, Whitesides GM, Carrilho E (2010) Diagnostics for the developing world: microfluidic paper-based analytical devices. Anal Chem 82:3–10

    Article  Google Scholar 

  • Matsuura K, Naruse K (2012) Use of silicone elastomer-based microfluidic devices and systems in reproductive technologies. In: Boczkowska A (ed) Advanced elastomers: technology, properties and applications. InTech, Rijeka, pp 243–262

    Google Scholar 

  • Matsuura K, Hayashi N, Takiue C, Hirata R, Habara T, Naruse K (2010) Blastocyst quality scoring based on morphologic grading correlates with cell number. Fertil Steril 94:1135–1137

    Article  Google Scholar 

  • Matsuura K, Kuroda Y, Yamashita K, Funahashi H (2011) Hydrophobic silicone elastomer chamber for recording trajectories of motile porcine sperms without adsorption. J Reprod Dev 57:163–167

    Article  Google Scholar 

  • Matsuura K, Takenami M, Kuroda Y, Hyakutake T, Yanase S, Naruse K (2012) Screening of sperm velocity by fluid mechanical characteristics of a cyclo-olefin polymer microfluidic sperm-sorting device. Reprod Biomed Online 24:109–115

    Article  Google Scholar 

  • McCormack MC, McCallum S, Behr B (2006) A novel microfluidic device for male subfertility screening. J Urol 175:2223–2227

    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 

  • Mota PC, Ramalho-Santos J (2006) Comparison between different markers for sperm quality in the cat: Diff-Quik as a simple optical technique to assess changes in the DNA of feline epididymal sperm. Theriogeneology 65:1360–1375

    Article  Google Scholar 

  • Nasr-Esfahani MH, Aboutorabi R, Esfandiari E, Mardani M (2002) Sperm MTT viability assay: a new method for evaluation of human sperm viability. J Assist Reprod Genet 19:477–482

    Article  Google Scholar 

  • Nwajiaku LA, Mbachu II, Ikeako L (2012) Prevalence, clinical pattern and major causes of male infertility in Nnewi, south east Nigeria: a five year review. Afrimedic J 3:16–19

    Google Scholar 

  • Pennings G, De Wert G, Shenfield F, Cohen J, Tarlatzis B, Devroey P (2009) Providing infertility treatment in resource-poor countries. Hum Reprod 24:1008–1011

    Article  Google Scholar 

  • Raty S, Davis J, Beebe D, Rodriguez-Zas S, Wheeler M (2001) Culture in microchannels enhances in vitro embryonic development of preimplantation mouse embryos. Theriogenology 55:241

    Google Scholar 

  • Raty S, Walters EM, Davis J, Zeringue H, Beebe DJ, Rodriguez-Zas SL, Wheeler MB (2004) Embryonic development in the mouse is enhanced via microchannel culture. Lab Chip 4:186–190

    Article  Google Scholar 

  • Rodríguez-Martínez H (2007) State of the art in farm animal sperm evaluation. Reprod Fertil Dev 19:91–101

    Article  Google Scholar 

  • Segerink LI, Sprenkels AJ, ter Braak PM, Vermes I, van den Berg A (2010) On-chip determination of spermatozoa concentration using electrical impedance measurements. Lab Chip 10:1018–1024

    Article  Google Scholar 

  • Sousa AP, Tavares RS, Velez de la Calle JF, Figueiredo H, Almeida V, Almeida-Santos T, Ramalho-Santos J (2009) Dual use of Diff-Quik-like stains for the simultaneous evaluation of human sperm morphology and chromatin status. Hum Reprod 24:28–36

    Article  Google Scholar 

  • Tsai T-T, Shen S-W, Cheng C-M, Chen C-F (2013) Paper-based tuberculosis diagnostic devices with colorimetric gold nanoparticles. Sci Technol Adv Mater 14:044404

    Article  Google Scholar 

  • van Balen F, Gerrits T (2001) Quality of infertility care in poor-resource areas and the introduction of new reproductive technologies. Hum Reprod 16:215–219

    Article  Google Scholar 

  • Vayena E, Rowe PJ, Peterson HB (2002) Assisted reproductive technology in developing countries: Why should we care? Fertil Steril 78:13–15

    Article  Google Scholar 

  • Wang H-K, Tsai C-H, Chen K-H, Tang C-T, Leou J-S, Li P-C, Tang Y-L, Hsieh H-J, Wu H-C, Cheng C-M (2013) Cellulose-based diagnostic devices for diagnosing serotype-2 dengue fever in human serum. Adv Health Mater. doi:10.1002/adhm.201300150

    Google Scholar 

  • Wong W-Y, Thomas CMG, Merkus JMWM, Zielhuis GA, Steegers-Theunissen RPM (2000) Male factor subfertility: possible causes and the impact of nutritional factors. Fertil Steril 73:435–442

    Article  Google Scholar 

  • Zeringue HC, Rutledge JJ, Beebe DJ (2005) Early mammalian embryo development depends on cumulus removal technique. Lab Chip 5:86–90

    Article  Google Scholar 

  • Zhang X, Khimji I, Gurkan UA, Safaee H, Catalano PN, Keles HO, Kayaalp E, Demirci U (2011) Lensless imaging for simultaneous microfluidic sperm monitoring and sorting. Lab Chip 11:2535–2540

    Article  Google Scholar 

Download references

Acknowledgments

This study was partly supported by a grant-in-aid for Scientific Research for Young Scientists (A), and Challenging Exploratory Research (No. 22680036 and 23650262 to K. M.), Special Coordination Funds for Promoting Sciences and Technology from the Ministry of Education Science, Sports and Culture, Japan, and Okayama Foundation for Science and Technology (to K. M.). The authors would also like to thank the National Science Council of Taiwan for financially supporting this research under Contract Nos. NSC 101-2628-E-007-011-MY3, NSC 102-2221-E-007-031, and the Grant for Interactive Nano/MicroElectroMechanical Components and Systems from National Tsing Hua University, Taiwan (to C.-M. C.). K. M. thanks Mieko Kodama (Okayama University) for her assistance with figure preparation and formatting.

Author information

Authors and Affiliations

  1. Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, 700-8558, Japan

    Koji Matsuura, Wenqian Li, Yuka Asano & Keiji Naruse

  2. Institute of Nanoengineering and Microsystems, National Tsing Hua University, Hsinchu, 30013, Taiwan

    Kuan-Hung Chen, Cheng-Han Tsai & Chao-Min Cheng

Authors
  1. Koji Matsuura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kuan-Hung Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheng-Han Tsai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenqian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuka Asano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Keiji Naruse
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Chao-Min Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chao-Min Cheng.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 864 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsuura, K., Chen, KH., Tsai, CH. et al. Paper-based diagnostic devices for evaluating the quality of human sperm. Microfluid Nanofluid 16, 857–867 (2014). https://doi.org/10.1007/s10404-014-1378-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10404-014-1378-y

Keywords

Search

Navigation