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.
Similar content being viewed by others
References
R. Baudoin, A. Corlu, L. Griscom, C. Legallais, E. Leclerc, Toxicol. In Vitro 21, 535 (2007) doi:10.1016/j.tiv.2006.11.004
K. Bhadriraju, C.S. Chen, Drug Discov. Today 7, 612 (2002) doi:10.1016/S1359-6446(02)02273-0
A.M. Christensen, D. Change-Yen, B.K. Gale, J. Micromech. Microeng. 15, 928 (2005) doi:10.1088/0960-1317/15/5/005
P.S. Dittrich, A. Manz, Nat. Rev. Drug Discov. 5, 210 (2006) doi:10.1038/nrd1985
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
J. El-Ali, P.K. Sorger, K.F. Jensen, Nature 442, 403 (2006) doi:10.1038/nature05063
R.J. Fisher, R.A. Peattie, Adv. Biochem. Eng. Biotechnol. 103, 1 (2007)
S. Haeberle, R. Zengerle, Lab Chip 7, 1094 (2007) doi:10.1039/b706364b
J.H. Kang, Y.C. Kim, J.K. Park, Lab Chip 8, 176 (2008) doi:10.1039/b712672g
T.M. Keenan, A. Folch, Lab Chip 8, 34 (2008) doi:10.1039/b711887b
L. Kim, Y.C. Toh, J. Voldman, H. Yu, Lab Chip 7, 681 (2007) doi:10.1039/b704602b
D. Kohlheyer, J.C. Eijkel, S. Schlautmann, A. van den Berg, R.B. Schasfoort, Anal. Chem. 80, 4111 (2008) doi:10.1021/ac800275c
E. Leclerc, Y. Sakai, T. Fujii, Biotechnol. Prog. 20, 750 (2004) doi:10.1021/bp0300568
D.D. Meng, J. Kim, C. Kim, J. Micromech. Microeng. 16, 419 (2006) doi:10.1088/0960-1317/16/2/028
T.H. Park, M.L. Shuler, Biotechnol. Prog. 19, 243 (2003) doi:10.1021/bp020143k
A. Sin, K.C. Chin, M.F. Jamil, Y. Kostov, G. Rao, M.L. Shuler, Biotechnol. Prog. 20, 338 (2004) doi:10.1021/bp034077d
A.M. Skelley, J. Voldman, Lab Chip 8, 1733 (2008) doi:10.1039/b807037g
J.H. Sung, M.L. Shuler, Lab Chip, in press (2009a) doi:10.1039/B901377F
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), accepted
D.A. Tatosian, M.L. Shuler, Biotech Bioeng, in press (2008) doi:10.1002/bit.22219
K. Viravaidya, A. Sin, M.L. Shuler, Biotechnol. Prog. 20, 316 (2004) doi:10.1021/bp0341996
G.M. Whitesides, Nature 442, 368 (2006) doi:10.1038/nature05058
Z. Yang, S. Matsumoto, R. Maeda, Sens. Actuators. A. Phys. 95, 274 (2002) doi:10.1016/S0924-4247(01)00741-5
L. Zheng, P.D. Yapa, J Hydraul Eng. 126, 852 (2000) doi:10.1061/(ASCE)0733-9429(2000)126:11(852)
Acknowledgements
This research was supported in part by Nanobiotechnology center [NBTC, project CM-2 (Nanotechnological Assessment of Drug Toxicity)], CNF (Cornell Nanoscale Science and Technology Facility), NSF (National Science Foundation), anonymous gift to Cornell Biomedical Engineering, and also partly by a grant from Army Corp of Engineers (CERL) W9132T-07. JHS gratefully acknowledges support from Samsung Lee Kun Hee Scholarship Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sung, J.H., Shuler, M.L. Prevention of air bubble formation in a microfluidic perfusion cell culture system using a microscale bubble trap. Biomed Microdevices 11, 731–738 (2009). https://doi.org/10.1007/s10544-009-9286-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10544-009-9286-8