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Development of the Microfluidic Device to Regulate Shear Stress Gradients

  • Kim, Tae Hyeon (Department of Mechanical Engineering, Sogang University) ;
  • Lee, Jong Min (Department of Mechanical Engineering, Sogang University) ;
  • Ahrberg, Christian D. (Research Center, Sogang University) ;
  • Chung, Bong Geun (Department of Mechanical Engineering, Sogang University)
  • Received : 2018.08.20
  • Accepted : 2018.10.07
  • Published : 2018.12.20

Abstract

Shear stress occurs in flowing liquids, especially at the interface of a flowing liquid and a stationary solid phase. Thus, it occurs inside the artery system of the human body, where it is responsible for a number of biological functions. The shear stress level generally remains less than $70dyne/cm^2$ in the whole circulatory system, but in the stenotic arteries, which are constricted by 95%, a shear stress greater than $1,000dyne/cm^2$ can be reached. Methods of researching the effects of shear stress on cells are of large interest to understand these processes. Here, we show the development of a microfluidic device for generating shear stress gradients. The performance of the shear stress gradient generator was theoretically simulated prior to experiments. Through simple manipulations of the liquid flow, the shape and magnitude of the shear stress gradients can be manipulated. Our microfluidic device consisted of five portions divided by arrays of micropillars. The generated shear stress gradient has five distinct levels at 8.38, 6.55, 4.42, 2.97, and $2.24dyne/cm^2$. Thereafter, an application of the microfluidic device was demonstrated testing the effect of shear stress on human umbilical vein endothelial cells.

Keywords

Acknowledgement

Supported by : National Research Foundation (NRF) of Korea, Sogang University

References

  1. Korin, N., Gounis, M.J., Wakhloo, A.K. & Ingber, D.E. Targeted Drug Delivery to Flow-Obstructed Blood Vessels Using Mechanically Activated Nanotherapeutics. JAMA Neurol. 72, 119-122 (2015). https://doi.org/10.1001/jamaneurol.2014.2886
  2. Chistiakov, D.A., Orekhov, A.N. & Bobryshev, Y.V. Effects of shear stress on endothelial cells: go with the flow. Acta Physiol. 219, 382-408 (2017). https://doi.org/10.1111/apha.12725
  3. Zhang, X., Jones, P. & Haswell, S.J. Attachment and detachment of living cells on modified microchannel surfaces in a microfluidic-based lab-on-a-chip system. Chem. Eng. J. 135, S82-88 (2008). https://doi.org/10.1016/j.cej.2007.07.054
  4. Plouffe, B.D. et al. Peptide-mediated selective adhesion of smooth muscle and endothelial cells in microfluidic shear flow. Langmuir 23, 5050-5055 (2007). https://doi.org/10.1021/la0700220
  5. Plouffe, B.D., Kniazeva, T., Mayer, J.E., Murthy, S.K. & Sales, V.L. Development of microfluidics as endothelial progenitor cell capture technology for cardiovascular tissue engineering and diagnostic medicine. FASEB J. 23, 3309-3314 (2009). https://doi.org/10.1096/fj.09-130260
  6. Sin, A., Murthy, S.K., Revzin, A., Tompkins, R.G. & Toner, M. Enrichment using antibody-coated microfluidic chambers in shear flow: model mixtures of human lymphocytes. Biotechnol. Bioeng. 91, 816-826 (2005). https://doi.org/10.1002/bit.20556
  7. Sorescu, G.P. et al. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response. J. Biol. Chem. 278, 31128-31135 (2003). https://doi.org/10.1074/jbc.M300703200
  8. Glen, K. et al. Modulation of functional responses of endothelial cells linked to angiogenesis and inflammation by shear stress: differential effects of the mechanotransducer CD31. J. Cell Physiol. 227, 2710-2721 (2012). https://doi.org/10.1002/jcp.23015
  9. Stolberg, S. & McCloskey, K.E. Can shear stress direct stem cell fate? Biotechnol. Progr. 25, 10-19 (2009). https://doi.org/10.1002/btpr.124
  10. Park, J. et al. Control of stem cell fate and function by engineering physical microenvironments. Intrgr. Biol. 4, 1008-1018 (2012). https://doi.org/10.1039/c2ib20080e
  11. Bowden, N. et al. Experimental Approaches to Study Endothelial Responses to Shear Stress. Antioxid. Redox Signal. 25, 389-400 (2016). https://doi.org/10.1089/ars.2015.6553
  12. Chiu, D.T. et al. Small but Perfectly Formed? Successes, Challenges, and Opportunities for Microfluidics in the Chemical and Biological Sciences. Chem. 2, 201-223 (2017). https://doi.org/10.1016/j.chempr.2017.01.009
  13. Kim, T.H., Lee, J.M., Chung, B.H. & Chung. B.G. Development of microfluidic LED sensor platform. Nano Converg. 2, 12 (2015). https://doi.org/10.1186/s40580-015-0043-9
  14. Kim, J.-y., Chang, S.-I. & O'Hare, D. Integration of monolithic porous polymer with droplet-based microfluidics on a chip for nano/picoliter volume sample analysis. Nano Converg. 1, 3 (2014). https://doi.org/10.1186/s40580-014-0003-9
  15. Panigrahi, P.K. Transport Phenomena in Microfluidic Systems: John Wiley & Sons, pp. 13-19 (2016).
  16. Yuki, T., Masayuki, Y., Teruo, O., Takehiko, K. & Kiichi, S. Evaluation of effects of shear stress on hepatocytes by a microchip-based system. Meas. Sci. Technol. 17, 3167 (2006). https://doi.org/10.1088/0957-0233/17/12/S08
  17. Gutierrez, E. & Groisman, A. Quantitative Measurements of the Strength of Adhesion of Human Neutrophils to a Substratum in a Microfluidic Device. Anal. Chem. 79, 2249-2258 (2007). https://doi.org/10.1021/ac061703n
  18. Rupprecht, P. et al. A tapered channel microfluidic device for comprehensive cell adhesion analysis, using measurements of detachment kinetics and shear stressdependent motion. Biomicrofluidics 6, 014107 (2012). https://doi.org/10.1063/1.3673802
  19. Kim, H.W., Han, S., Kim, W., Lim, J. & Kim, D.S. Modulating wall shear stress gradient via equilateral triangular channel for in situ cellular adhesion assay. Biomicrofluidics 10, 054119 (2016). https://doi.org/10.1063/1.4965822
  20. Chen, W.-M. et al. A novel gait platform to measure isolated plantar metatarsal forces during walking. J. Biomech. 43, 2017-2021 (2010). https://doi.org/10.1016/j.jbiomech.2010.03.036
  21. Karki, S., Lekkala, J., Kuokkanen, H. & Halttunen, J. Development of a piezoelectric polymer film sensor for plantar normal and shear stress measurements. Sens. Actuators A Phys. 154, 57-64 (2009). https://doi.org/10.1016/j.sna.2009.07.010
  22. Heywood, E.J., Jeutter, D.C. & Harris, G.F. Tri-axial plantar pressure sensor: design, calibration and characterization. The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, pp. 2010-2013 (2004).
  23. Rajala, S. & Lekkala, J. Plantar shear stress measurements - A review. Clin. Biomech. 29, 475-483 (2014). https://doi.org/10.1016/j.clinbiomech.2014.04.009
  24. Gnanamanickam, E.P., Nottebrock, B., Grosse, S., Sullivan, J.P. & Schroder, W. Measurement of turbulent wall shear-stress using micro-pillars. Meas. Sci. Technol. 24, 124002 (2013). https://doi.org/10.1088/0957-0233/24/12/124002
  25. Green, J.V. et al. Effect of channel geometry on cell adhesion in microfluidic devices. Lab Chip 9, 677-685 (2009). https://doi.org/10.1039/B813516A
  26. Lee, J.M., Kim, J.-e., Kang, E., Lee, S.-H. & Chung, B.G. An integrated microfluidic culture device to regulate endothelial cell differentiation from embryonic stem cells. Electrophoresis 32, 3133-3137 (2011). https://doi.org/10.1002/elps.201100161
  27. Galie, P., Van Oosten, A., Chen, C. & Janmey, P. Application of multiple levels of fluid shear stress to endothelial cells plated on polyacrylamide gels. Lab Chip 15, 1205-1212 (2015). https://doi.org/10.1039/C4LC01236D
  28. Back, L.H., Radbill, J.R., Cho, Y.I. & Crawford, D.W. Measurement and prediction of flow through a replica segment of a mildly atherosclerotic coronary artery of man. J. Biomech. 19, 1-17 (1986). https://doi.org/10.1016/0021-9290(86)90104-1
  29. Saxena, A., Ng, E. & Raman, V. Thermographic venous blood flow characterization with external cooling stimulation. Infrared Phys. Technol. 90, 8-19 (2018). https://doi.org/10.1016/j.infrared.2018.02.001
  30. Inoguchi, H., Tanaka, T., Maehara, Y. & Matsuda, T. The effect of gradually graded shear stress on the morphological integrity of a huvec-seeded compliant small-diameter vascular graft. Biomaterials 28, 486-495 (2007). https://doi.org/10.1016/j.biomaterials.2006.09.020
  31. Abu-Reesh, I. & Kargi, F. Biological responses of hybridoma cells to defined hydrodynamic shear stress. J. Biotechnol. 9, 167-178 (1989). https://doi.org/10.1016/0168-1656(89)90106-5
  32. Bruus, H. Acoustofluidics 1: Governing equations in microfluidics. Lab Chip 11, 3742-3751 (2011). https://doi.org/10.1039/c1lc20658c
  33. Duffy, D.C., McDonald, J.C., Schueller, O.J.A. & Whitesides, G.M. Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). Anal. Chem. 70, 4974-4984 (1998). https://doi.org/10.1021/ac980656z
  34. Choi, J.W. et al. Dual-nozzle microfluidic droplet generator. Nano Converg. 5, 12 (2018). https://doi.org/10.1186/s40580-018-0145-2
  35. Choi, J.-H. et al. Priming nanoparticle-guided diagnostics and therapeutics towards human organs-on-a-chips microphyiological system. Nano Converg. 6, 24 (2016).
  36. Kim, J.-Y., Chang, S.-I., deMello, A.J. & O'Hare, D. Integration of monolithic porous polymer with droplet- based microfluidics on a chip for nano/picoliter volume sample analysis. Nano Converg. 1, 3 (2014). https://doi.org/10.1186/s40580-014-0003-9

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