Biomedical Microdevices

, Volume 11, Issue 4, pp 731–738 | Cite as

Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap

Article

Abstract

Formation of air bubbles is a serious obstacle to a successful operation of a long-term microfluidic systems using cell culture. We developed a microscale bubble trap that can be integrated with a microfluidic device to prevent air bubbles from entering the device. It consists of two PDMS (polydimethyldisiloxane) layers, a top layer providing barriers for blocking bubbles and a bottom layer providing alternative fluidic paths. Rather than relying solely on the buoyancy of air bubbles, bubbles are physically trapped and prevented from entering a microfluidic device. Two different modes of a bubble trap were fabricated, an independent module that is connected to the main microfluidic system by tubes, and a bubble trap integrated with a main system. The bubble trap was tested for the efficiency of bubble capture, and for potential effects a bubble trap may have on fluid flow pattern. The bubble trap was able to efficiently trap air bubbles of up to 10 μl volume, and the presence of captured air bubbles did not cause alterations in the flow pattern. The performance of the bubble trap in a long-term cell culture with medium recirculation was examined by culturing a hepatoma cell line in a microfluidic cell culture device. This bubble trap can be useful for enhancing the consistency of microfluidic perfusion cell culture operation.

Keywords

Microfluidics Mammalian cell culture Bubble trap 

References

  1. R. Baudoin, A. Corlu, L. Griscom, C. Legallais, E. Leclerc, Toxicol. In Vitro 21, 535 (2007) doi:10.1016/j.tiv.2006.11.004 CrossRefGoogle Scholar
  2. K. Bhadriraju, C.S. Chen, Drug Discov. Today 7, 612 (2002) doi:10.1016/S1359-6446(02)02273-0 CrossRefGoogle Scholar
  3. A.M. Christensen, D. Change-Yen, B.K. Gale, J. Micromech. Microeng. 15, 928 (2005) doi:10.1088/0960-1317/15/5/005 CrossRefGoogle Scholar
  4. P.S. Dittrich, A. Manz, Nat. Rev. Drug Discov. 5, 210 (2006) doi:10.1038/nrd1985 CrossRefGoogle Scholar
  5. D. Eddington, Chips & Tips: In-line microfluidic bubble trap. (Lab Chip). http://www.rsc.org/Publishing/Journals/lc/bubble_trap.asp. Accessed 25 Nov 2008
  6. J. El-Ali, P.K. Sorger, K.F. Jensen, Nature 442, 403 (2006) doi:10.1038/nature05063 CrossRefGoogle Scholar
  7. R.J. Fisher, R.A. Peattie, Adv. Biochem. Eng. Biotechnol. 103, 1 (2007)Google Scholar
  8. S. Haeberle, R. Zengerle, Lab Chip 7, 1094 (2007) doi:10.1039/b706364b CrossRefGoogle Scholar
  9. J.H. Kang, Y.C. Kim, J.K. Park, Lab Chip 8, 176 (2008) doi:10.1039/b712672g CrossRefGoogle Scholar
  10. T.M. Keenan, A. Folch, Lab Chip 8, 34 (2008) doi:10.1039/b711887b CrossRefGoogle Scholar
  11. L. Kim, Y.C. Toh, J. Voldman, H. Yu, Lab Chip 7, 681 (2007) doi:10.1039/b704602b CrossRefGoogle Scholar
  12. D. Kohlheyer, J.C. Eijkel, S. Schlautmann, A. van den Berg, R.B. Schasfoort, Anal. Chem. 80, 4111 (2008) doi:10.1021/ac800275c CrossRefGoogle Scholar
  13. E. Leclerc, Y. Sakai, T. Fujii, Biotechnol. Prog. 20, 750 (2004) doi:10.1021/bp0300568 CrossRefGoogle Scholar
  14. D.D. Meng, J. Kim, C. Kim, J. Micromech. Microeng. 16, 419 (2006) doi:10.1088/0960-1317/16/2/028 CrossRefGoogle Scholar
  15. T.H. Park, M.L. Shuler, Biotechnol. Prog. 19, 243 (2003) doi:10.1021/bp020143k CrossRefGoogle Scholar
  16. A. Sin, K.C. Chin, M.F. Jamil, Y. Kostov, G. Rao, M.L. Shuler, Biotechnol. Prog. 20, 338 (2004) doi:10.1021/bp034077d CrossRefGoogle Scholar
  17. A.M. Skelley, J. Voldman, Lab Chip 8, 1733 (2008) doi:10.1039/b807037g CrossRefGoogle Scholar
  18. J.H. Sung, M.L. Shuler, Lab Chip, in press (2009a) doi:10.1039/B901377F
  19. J.H. Sung, M.L. Shuler, in Microdevices in Biology and Medicine (Methods in Bioengineering Series), ed. by Y. Nahmias, S.N. Bhatia (Artech House, Norwood, MA) (2009b), acceptedGoogle Scholar
  20. D.A. Tatosian, M.L. Shuler, Biotech Bioeng, in press (2008) doi:10.1002/bit.22219
  21. K. Viravaidya, A. Sin, M.L. Shuler, Biotechnol. Prog. 20, 316 (2004) doi:10.1021/bp0341996 CrossRefGoogle Scholar
  22. G.M. Whitesides, Nature 442, 368 (2006) doi:10.1038/nature05058 CrossRefGoogle Scholar
  23. Z. Yang, S. Matsumoto, R. Maeda, Sens. Actuators. A. Phys. 95, 274 (2002) doi:10.1016/S0924-4247(01)00741-5 CrossRefGoogle Scholar
  24. L. Zheng, P.D. Yapa, J Hydraul Eng. 126, 852 (2000) doi:10.1061/(ASCE)0733-9429(2000)126:11(852) CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.School of Chemical and Biomolecular EngineeringCornell UniversityIthacaUSA
  2. 2.Department of Biomedical EngineeringCornell UniversityIthacaUSA

Personalised recommendations