Skip to main content
SpringerLink
Log in

Analysis of Thrombosis Formation and Growth Using Microfluidic Chips and Multiphase Computational Fluid Dynamics

  • Original Article
  • Published:
BioChip Journal Aims and scope Submit manuscript

Abstract

Thrombosis is a vascular disease associated with severe risks such as heart attack and stroke. Extensive research has been conducted worldwide to identify the underlying causes of thrombus formation due to its potential implications. Many thrombosis studies have investigated hemodynamic effects by assuming blood as a single-phase fluid. However, since the behavior of blood is greatly influenced by red blood cells (RBCs), it is necessary to analyze blood as a mixture (two-phase). In this paper, computational fluid dynamics (CFD) was performed assuming that blood is a two-phase fluid composed of plasma and RBCs. In addition, microchannels with circular cross-sections similar to human blood vessels were fabricated and used for blood experiments. The thrombus formed in the microchannel was visualized using image processing technology. Three-dimensional models incorporating the visualized thrombus were created and utilized to investigate the physical factors affecting the thrombus surface. In conditions where the shear rates were too high, the thrombus did not grow because of the drag force. Thrombus overcame the drag force and grew in areas with reduced shear stress. Also, the volume fraction of plasma calculated by the two-phase fluid model increased after the apex of stenosis and behind the thrombus. Thrombus growth was identified in areas with increased plasma volume fraction.

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

Access this article

Log in via an institution

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Availability of Data and Materials

All data generated or analyzed during this study are included in this published article.

Abbreviations

CFD:

Computational fluid dynamics

vWF:

Von Willebrand factor

RBCs:

Red blood cells

PDMS:

Polydimethylsiloxane

References

  1. Raskob, G.E., et al.: Thrombosis. Arterioscler Thromb Vasc Biol 34(11), 2363–2371 (2014). https://doi.org/10.1161/ATVBAHA.114.304488

    Article  CAS  PubMed  Google Scholar 

  2. Darvall, K.A.L., Sam, R.C., Silverman, S.H., Bradbury, A.W., Adam, D.J.: Obesity and thrombosis. Eur J Vasc Endovasc Surg 33(2), 223–233 (2007). https://doi.org/10.1016/J.EJVS.2006.10.006

    Article  CAS  PubMed  Google Scholar 

  3. Vaidya, A.R., Wolska, N., Vara, D., Mailer, R.K., Schröder, K., Pula, G.: Diabetes and thrombosis: a central role for vascular oxidative stress. Antioxidants (2021). https://doi.org/10.3390/ANTIOX10050706

    Article  PubMed  PubMed Central  Google Scholar 

  4. Huang, L., Li, J., Jiang, Y.: Association between hypertension and deep vein thrombosis after orthopedic surgery: a meta-analysis. Eur J Med Res 21(1), 13 (2016). https://doi.org/10.1186/S40001-016-0207-Z

    Article  PubMed  PubMed Central  Google Scholar 

  5. Barua, R.S., Ambrose, J.A.: Mechanisms of coronary thrombosis in cigarette smoke exposure. Arterioscler Thromb Vasc Biol 33(7), 1460–1467 (2013). https://doi.org/10.1161/ATVBAHA.112.300154

    Article  CAS  PubMed  Google Scholar 

  6. Bark, D.L., Ku, D.N.: Wall shear over high degree stenoses pertinent to atherothrombosis. J Biomech 43(15), 2970–2977 (2010). https://doi.org/10.1016/j.jbiomech.2010.07.011

    Article  PubMed  Google Scholar 

  7. Nesbitt, W.S., et al.: A shear gradient-dependent platelet aggregation mechanism drives thrombus formation. Nat Med 15(6), 665–673 (2009). https://doi.org/10.1038/nm.1955

    Article  CAS  PubMed  Google Scholar 

  8. Para, A., Bark, D., Lin, A., Ku, D.: Rapid platelet accumulation leading to thrombotic occlusion. Ann Biomed Eng 39(7), 1961–1971 (2011). https://doi.org/10.1007/s10439-011-0296-3

    Article  CAS  PubMed  Google Scholar 

  9. Casa, L.D.C., Deaton, D.H., Ku, D.N.: Role of high shear rate in thrombosis. J Vasc Surg 61(4), 1068–1080 (2015). https://doi.org/10.1016/j.jvs.2014.12.050

    Article  PubMed  Google Scholar 

  10. Wootton, D.M., Markou, C.P., Hanson, S.R., Ku, D.N.: A mechanistic model of acute platelet accumulation in thrombogenic stenoses. Ann Biomed Eng 29(4), 321–329 (2001). https://doi.org/10.1114/1.1359449

    Article  CAS  PubMed  Google Scholar 

  11. Zhao, Y.C., et al.: Hemodynamic analysis for stenosis microfluidic model of thrombosis with refined computational fluid dynamics simulation. Sci Rep (2021). https://doi.org/10.1038/s41598-021-86310-2

    Article  PubMed  PubMed Central  Google Scholar 

  12. Asif, A., et al.: Inflow stenosis in arteriovenous fistulas and grafts: a multicenter, prospective study. Kidney Int 67(5), 1986–1992 (2005). https://doi.org/10.1111/j.1523-1755.2005.00299.x

    Article  PubMed  Google Scholar 

  13. Westein, E., Van Der Meer, A.D., Kuijpers, M.J.E., Frimat, J.P., Van Den Berg, A., Heemskerk, J.W.M.: Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner. Proc Natl Acad Sci U S A 110(4), 1357–1362 (2013). https://doi.org/10.1073/pnas.1209905110

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hastings, S.M., Griffin, M.T., Ku, D.N.: Hemodynamic studies of platelet thrombosis using microfluidics. Platelets 28(5), 427–433 (2017). https://doi.org/10.1080/09537104.2017.1316483

    Article  CAS  PubMed  Google Scholar 

  15. Chen, Y., et al.: Reduction of Erythrocyte Fluid Adaptability Due to Cell Membrane Hardening Based on Single-Cell Analysis. Biochip J 15(1), 90–99 (2021). https://doi.org/10.1007/s13206-021-00005-4

    Article  CAS  Google Scholar 

  16. Pollet, A.M.A.O., Homburg, E.F.G.A., Cardinaels, R., den Toonder, J.M.J.: 3D sugar printing of networks mimicking the vasculature. Micromachines (Basel). (2020). https://doi.org/10.3390/mi11010043

    Article  Google Scholar 

  17. Chung, A.J.: A minireview on inertial microfluidics fundamentals: inertial particle focusing and secondary flow. BioChip J. 13(1), 53–63 (2019). https://doi.org/10.1007/s13206-019-3110-1

    Article  CAS  Google Scholar 

  18. Qiao, Y., Zeng, Y., Ding, Y., Fan, J., Luo, K., Zhu, T.: Numerical simulation of two-phase non-Newtonian blood flow with fluid-structure interaction in aortic dissection. Comput Methods Biomech Biomed Engin 22(6), 620–630 (2019). https://doi.org/10.1080/10255842.2019.1577398

    Article  PubMed  Google Scholar 

  19. Flores Marcial, H.B., et al.: Influence of multiple stenoses on thrombosis formation: an in vitro study. Micro Nano Syst Lett (2022). https://doi.org/10.1186/s40486-022-00159-2

    Article  Google Scholar 

  20. Choi, J.-S., et al.: Quantitative image analysis of thrombus formation in microfluidic in-vitro models. Micro Nano Syst Lett (2022). https://doi.org/10.1186/s40486-022-00166-3

    Article  Google Scholar 

  21. Nguyen, T.Q., Park, W.T.: Fabrication method of multi-depth circular microchannels for investigating arterial thrombosis-on-a-chip. Sens Actuators B Chem (2020). https://doi.org/10.1016/j.snb.2020.128590

    Article  PubMed  PubMed Central  Google Scholar 

  22. Nguyen, T.Q., Park, W.T.: Rapid, low-cost fabrication of circular microchannels by air expansion into partially cured polymer. Sens Actuators B Chem 235, 302–308 (2016). https://doi.org/10.1016/j.snb.2016.05.008

    Article  CAS  Google Scholar 

  23. Alexy, T., et al.: Physical properties of blood and their relationship to clinical conditions. Front Physiol. (2022). https://doi.org/10.3389/fphys.2022.906768

    Article  PubMed  PubMed Central  Google Scholar 

  24. Al-Azawy, M.G., Kadhim, S.K., Hameed, A.S.: Newtonian and non-newtonian blood rheology inside a model of stenosis. CFD Lett. 12(11), 27–36 (2020). https://doi.org/10.37934/cfdl.12.11.2736

    Article  Google Scholar 

  25. Ascolese, M., Farina, A., Fasano, A.: The Fåhræus–Lindqvist effect in small blood vessels: how does it help the heart? J Biol Phys 45(4), 379–394 (2019). https://doi.org/10.1007/s10867-019-09534-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Not applicable.

Funding

This study was conducted with the support of the National Research Foundation of Korea (2020R1F1A107499512).

Author information

Authors and Affiliations

  1. Department of Mechanical Engineering, Seoul National University of Science and Technology, Seoul, Republic of Korea

    Dong-Hwi Ham, Ji-Seob Choi, Pyeong-Ho Jeong, Jung-Hyun Kim & Woo-Tae Park

  2. Convergence Institute of Biomedical Engineering and Biomaterials, Seoul National University of Science and Technology, Seoul, Republic of Korea

    Helem Betsua Flores Marcial

  3. Samsung Medical Center, Seoul, Republic of Korea

    Jin-Ho Choi

Authors
  1. Dong-Hwi Ham
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ji-Seob Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pyeong-Ho Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jung-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Helem Betsua Flores Marcial
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jin-Ho Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Woo-Tae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WTP supervised the fundings of this work and reviewed the manuscript. DHH, JSC, JHK, PHJ, and HBFM fabricated the device. JHC, WTP, DHH, JSC, and HBFM designed the scope and performed the experiments. DHH drafted the manuscript. WTP read and approved the final manuscript.

Corresponding author

Correspondence to Woo-Tae Park.

Ethics declarations

Conflict of Interest

The authors declare that they have no competing interests.

Ethics Approval

This study was conducted after approval by the Seoul National University of Science and Technology IRB (2020–0025-01).

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ham, DH., Choi, JS., Jeong, PH. et al. Analysis of Thrombosis Formation and Growth Using Microfluidic Chips and Multiphase Computational Fluid Dynamics. BioChip J 17, 478–486 (2023). https://doi.org/10.1007/s13206-023-00123-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13206-023-00123-1

Keywords

Search

Navigation