H2020 PROGRAM | MicroFSMA
MicroFSMA – Microfluidic based platform for SeMen Analysis
SEMEN ANANLYSIS STATE OF THE ART AND SIGNIFICANCE
Semen analysis has always been an important step to diagnose male infertility. Clinical andrologists/embryologists assess semen sample using motility of the sperm cell. Sperm motility is triggered by synergistic interplay of cytoskeleton and motor proteins accompanying with other supplementary molecules. Any flaw in the basic structure and working of these proteins would cause male infertility. ICSI (Intra Cytoplasmic Sperm Injection), GIFT (Gamete Intra Fallopian Transfer) techniques are available for In-vitro fertilization (IVF). Sperm cells for IVF are selected by either conventional World Health Organization (WHO)’s protocol , or commercial Computer Assisted Semen Analysis (CASA) [2–4] or a combination of both .
However, these established methods study sperm motility and kinematics in an environment that significantly differs from in-vivo conditions. Although the three primary mechanisms viz. chemotaxis, thermotaxis, and rheotaxis are well known to direct human sperm cell towards female oocytes , but the biochemical and mechanical aspects of sperm cells swimming are not included in both methods. Additionally, the conventional method is laborious and time-consuming , and computer assisted results have been observed to lack reproducibility when multiple screening is carried out for the same sample .
SEMEN ANALYSIS ON A CHIP: PROJECT INSIGHT
Microfluidics is an alternative technology that could aid in sperm motility analysis and potential sperm isolation for IVF. It has been already demonstrated that microchannels can be employed to assess sperm motility alike computer assisted systems . Over the decade, microfluidic devices have been emerged to control and impersonate the chemical and physical environment for a variety of biological cell types. As a result, microfluidics chips have been established successfully to recognize responsive sperm cells towards chemical [10–13] and thermal [14, 15] gradient.
Nevertheless, there are significant gaps which avert the dissemination and regulatory acceptance of microfluidic-based semen analysis over Computer Assisted Semen Analysis: (i). lack of standardization; (ii). absence of a user-friendly platform. Standardization and a user-friendly platform encourage the laboratories to adopt the invention.
MicroFSMA involves developing a microfluidic-based assay to isolate quality sperm for assisted conception. The technology will contain microfluidic chips integrated with a computational framework. Microfluidics chips will be designed to replicate the in-vivo physical and chemical environment of a female reproductive tract. Additionally, a computer program will facilitate multi-sperm head and flagella tracking for the recorded time-lapse image sequence. Tracking algorithm will connect the positions of sperm cells in recorded successive images, and subsequently the quantitative analysis of sperm cell kinematics will be carried out (figure 1).
Figure 1: A pictorial overview of MicroFSMA. Collected semen specimen from the male patients will be screened using the microfluidic devices. Image data will be analyzed using an automated computational framework, and sperm kinematics along with sperm motility will be reported.
SPERM CELL PHYSIOLOGY
FIELD OF APPLICATIONS
IN-VITRO FERTILIZATION (IVF)
SEMEN ANALYSIS: INNOVATION
Sperm cells commonly move in a straightforward direction with the symmetrical flagellar wave. In the presence of the chemical/physical stimulus, responsive sperm cells adjust their flagellar beating to an asymmetric pattern and move towards the positive gradient by creating helical trajectory pattern. These adjustments in flagellar beating occur due to the [Ca++] regulation in sperm cells. Analysis of asymmetry in the presence of chemical and physical stimulus will lead to recognizing the novel parameters for assessment of semen sample. Incorporation of asymmetry will enable the evaluation of parameters which manipulate the progression of sperm cells.
MITIGATING THE RISKS ASSOCIATED WITH IVF
Failure rates of IVF have been primarily ascribed to the use of poor quality sperm. Hence, the isolation of good quality sperm since sperm quality directly governs the fertilization process of the oocyte is pivotal to IVF. Random selection of sperm cells leads to flawed embryos, which comprises high failure rates, multiple pregnancies, miscarriage, and premature birth in IVF. MicroFSMA aims to alleviate the risks allied to IVF. Accounting natural manipulators in the progression of sperm cells will reduce the failure risk for IVF.
SPREADING THE MESSAGE
The European Commission is actively promoting innovation throughout a significant amount of economic efforts. Nevertheless, those are often unreported or poorly understood by the general community outreach. Considering the potential impact of MicroFSMA in the field with high ethical significance, the meaning and the results achieved by the project will be disseminated to the general outreach through selected articles in magazines as well as promoting a dedicated symposium in a scientific festival.
The project manager: Dr. Shiva K Shukla
Dr. Shukla is a Marrie Currie IF Fellow. His research work is focused on the development of miniaturized devices for clinical diagnosis.
Dr. Shukla will be engaged in the different perspectives and roles involved in entrepreneurship and R&D. The outcomes of these actions will provide Dr. Shukla an in-depth comprehension related to the bridging of academia and industries.
Dr. ANTONI HOMS CORBERA
CTO (CHIEF TECHNOLOGY OFFICER)
DR. SHIVA K SHUKLA
R&D project manager
Dr. PIERRE GAUDRIAULT
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 842299
Disclaimer: this content reflects only the author’s view and the EU Agency is not responsible for the information it contains.
- World Health Organization, WHO laboratory manual for the examination and processing of human semen. 5th ed. 2010, Switzerland: World Health Organization.
- D, M., Objective analysis of sperm motility and kinematics. In: Keel BA, Webster BW, editors. Handbook of the Laboratory Diagnosis and Treatment of Infertility. Boca Raton: CRC Press, Inc, 1990: p. 97-133.
- Amann, R.P. and D. Waberski, Computer-assisted sperm analysis (CASA): Capabilities and potential developments. Theriogenology, 2014. 81(1): p. 5-17.e3.
- Broekhuijse, M.L.W.J., et al., Additional value of computer assisted semen analysis (CASA) compared to conventional motility assessments in pig artificial insemination. Theriogenology, 2011. 76(8): p. 1473-1486.e1.
- Elsayed, M., T.M. El-Sherry, and M. Abdelgawad, Development of computer-assisted sperm analysis plugin for analyzing sperm motion in microfluidic environments using Image-J. Theriogenology, 2015. 84(8): p. 1367-77.
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- Urbano, L.F., et al., Automatic Tracking and Motility Analysis of Human Sperm in Time-Lapse Images. IEEE Trans Med Imaging, 2017. 36(3): p. 792-801.
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- Shiva, K.S., et al., Automated analysis of rat sperm motility in microchannels. Biomedical Physics & Engineering Express, 2018. 4(3): p. 035013.
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- Li, Z., et al., The construction of an interfacial valve-based microfluidic chip for thermotaxis evaluation of human sperm. Biomicrofluidics, 2014. 8(2): p. 024102.
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