Biomedical Microdevices

, Volume 13, Issue 3, pp 493–501 | Cite as

“Artificial micro organs”—a microfluidic device for dielectrophoretic assembly of liver sinusoids

  • Julia Schütte
  • Britta Hagmeyer
  • Felix Holzner
  • Massimo Kubon
  • Simon Werner
  • Christian Freudigmann
  • Karin Benz
  • Jan Böttger
  • Rolf Gebhardt
  • Holger Becker
  • Martin Stelzle
Article

Abstract

In order to study possible toxic side effects of potential drug compounds in vitro a reliable test system is needed. Predicting liver toxicity presents a major challenge of particular importance as liver cells grown in a cell culture suffer from a rapid loss of their liver specific functions. Therefore we are developing a new microfluidic test system for liver toxicity. This test system is based on an organ-like liver 3D co-culture of hepatocytes and endothelial cells. We devised a microfluidic chip featuring cell culture chambers with integrated electrodes for the assembly of liver sinusoids by dielectrophoresis. Fluid channels enable an organ-like perfusion with culture media and test compounds. Different chamber designs were studied and optimized with regard to dielectrophoretic force distribution, hydrodynamic flow profile, and cell trapping rate using numeric simulations. Based on simulation results a microchip was injection-moulded from COP. This chip allowed the assembly of viable hepatocytes and endothelial cells in a sinusoid-like fashion.

Keywords

Dielectrophoresis Multiphysics simulations Liver sinusoid 3D co-culture Micro-fluidics 

References

  1. P. Chao, T. Maguire, E. Novik, K.C. Cheng, M.L. Yarmush, Biochem. Pharmacol. 78, 625–632 (2009)CrossRefGoogle Scholar
  2. E.B. Cummings, A.K. Singh, Anal. Chem. 75, 4724–4731 (2003)CrossRefGoogle Scholar
  3. K. Domansky, W. Inman, J. Serdy, A. Dash, M.H.M. Lim, L.G. Griffith, Lab Chip 10, 51–58 (2010)CrossRefGoogle Scholar
  4. G. Fuhr, P. Rösch, T. Müller, V. Dressler, H. Göring, Plant Cell Physiol. 31, 975–985 (1990)Google Scholar
  5. R. Gebhardt, A. Hovhannisyan, Dev. Dyn. 239, 45–55 (2010)Google Scholar
  6. R. Gebhardt, J.G. Hengstler, D. Muller, R. Glockner, P. Buenning, B. Laube, E. Schmelzer, M. Ullrich, D. Utesch, N. Hewitt, M. Ringel, B.R. Hilz, A. Bader, A. Langsch, T. Koose, H.J. Burger, J. Maas, F. Oesch, Drug Metab. Rev. 35, 145–213 (2003)CrossRefGoogle Scholar
  7. L.J. Gershell, J.H. Atkins, Nat. Rev. Drug Discov. 2, 321–327 (2003)CrossRefGoogle Scholar
  8. C.-T. Ho, R.-Z. Lin, W.-Y. Chang, H.-Y. Chang, C.-H. Liu, Lab Chip 6, 724–734 (2006)CrossRefGoogle Scholar
  9. T.B. Jones, Electro mechanics of particles (Cambridge University Press, Cambridge, 1995)CrossRefGoogle Scholar
  10. B.H. Lapizco-Encinas, B.A. Simmons, E.B. Cummings, Y. Fintschenko, Anal. Chem. 76, 1571–1579 (2004)CrossRefGoogle Scholar
  11. B.H. Lapizco-Encinas, R.V. Davalos, B.A. Simmons, E.B. Cummings, Y. Fintschenko, J. Microbiol, Meth. 62, 317–326 (2005)Google Scholar
  12. S.W. Lee, S.D. Yang, Y.W. Kim, Y.K. Kim, in Eng. Med. Biol. Soc., Proc. 16th Annual International Conf. IEEE, Baltimore, MD, USA, 1994, pp. 1019–1020Google Scholar
  13. S. Masuda, M. Washizu, T. Nanba, IEEE Trans. Ind. Appl. 25, 732–737 (1989)CrossRefGoogle Scholar
  14. O. Morin, C. Normand, J. Cell, Physiol. 129, 103–110 (1986)Google Scholar
  15. R. Pethig, Crit. Rev. Biotechnol. 16(4), 331–348 (1996)CrossRefGoogle Scholar
  16. R. Pethig, G.H. Markx, Trends Biotechnol. 15, 426–431 (1997)CrossRefGoogle Scholar
  17. H.A. Pohl, Dielectrophoresis (Cambridge University Press, New York, 1978)Google Scholar
  18. M.J. Powers, K. Domansky, M.R. Kaazempur-Mofrad, A. Kalezi, A. Capitano, A. Upadhyaya, P. Kurzawski, K.E. Wack, D.B. Stolz, R. Kamm, L.G. Griffith, Biotechnol. Bioeng. 78, 257–269 (2002)CrossRefGoogle Scholar
  19. P.P.C. Poyck, R. Hoekstra, J.L.M. Vermeulen, A. van Wijk, R. Chamuleau, T.B.M. Hakvoort, T.M. van Gulik, W.H. Lamers, Cells Tissues Organs 188, 259–269 (2008)CrossRefGoogle Scholar
  20. J. Schütte, C. Freudigmann, K. Benz, J. Böttger, R. Gebhardt, M. Stelzle, Lab Chip, 2010Google Scholar
  21. A. Sivaraman, J.K. Leach, S. Townsend, T. Iida, B.J. Hogan, D.B. Stolz, R. Fry, L.D. Samson, S.R. Tannenbaum, L.G. Griffith, Curr. Drug Metab. 6, 569–591 (2005)CrossRefGoogle Scholar
  22. R.J. Thomas, R. Bhandari, D.A. Barrett, A.J. Bennett, J.R. Fry, D. Powe, B.J. Thomson, K.M. Shakesheff, Cells Tissues Organs 181, 67–79 (2005)CrossRefGoogle Scholar
  23. Y.C. Toh, C. Zhang, J. Zhang, Y.M. Khong, S. Chang, V.D. Samper, D. van Noort, D.W. Hutmacher, H. Yu, Lab Chip 7, 302–309 (2007)CrossRefGoogle Scholar
  24. Y.C. Toh, T.C. Lim, D. Tai, G. Xiao, D. van Noort, H. Yu, Lab Chip 9, 2026–2035 (2009)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Julia Schütte
    • 1
  • Britta Hagmeyer
    • 1
  • Felix Holzner
    • 1
  • Massimo Kubon
    • 1
  • Simon Werner
    • 1
  • Christian Freudigmann
    • 1
  • Karin Benz
    • 1
  • Jan Böttger
    • 2
  • Rolf Gebhardt
    • 2
  • Holger Becker
    • 3
  • Martin Stelzle
    • 1
  1. 1.NMI Naturwissenschaftliches und Medizinisches Institut an der Universität TübingenReutlingenGermany
  2. 2.Institut für BiochemieMedizinische Fakultät Universität LeipzigLeipzigGermany
  3. 3.Microfluidic ChipShop GmbHJenaGermany

Personalised recommendations