Abstract
This study reports a new microfluidic cell culture platform for real-time, in vitro microscopic observation and evaluation of cellular functions. Microheaters, a micro temperature sensor, and micropumps are integrated into the system to achieve a self-contained, perfusion-based, cell culture microenvironment. The key feature of the platform includes a unique, ultra-thin, culture chamber with a depth of 180 μm, allowing for real-time, high-resolution cellular imaging by combining bright field and fluorescent optics to visualize nanoparticle-cell/organelle interactions. The cell plating, culturing, harvesting and replenishing processes are performed automatically. The developed platform also enables drug screening and real-time, in situ investigation of the cellular and sub-cellular delivery process of nano vectors. The mitotic activity and the interaction between cells and the nano drug carriers (conjugated quantum dots-epirubicin) are successfully monitored in this device. This developed system could be a promising platform for a wide variety of applications such as high-throughput, cell-based studies and as a diagnostic cellular imaging system.
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Abbreviations
- Au:
-
gold
- CCD:
-
Charge-coupled device
- DOF:
-
Depth of field
- EMV:
-
Electromagnetic valve
- FBS:
-
Fetal bovine serum
- HEPES:
-
4-(2-hydroxyethyl)-1-piperazineethanesulfonic Acid
- ITO:
-
Indium-tin-oxide
- MTT:
-
3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium Bromide
- OC-2:
-
Oral cancer cell
- PDMS:
-
Polydimethylsiloxane
- Pt:
-
Platinum
- QD:
-
Quantum dots
- S-shape:
-
Serpentine-shape
References
P. Lang, K. Yeow, A. Nichols, A. Scheer, Nat. Rev. Drug Discov. 5, 343–356 (2006). doi:10.1038/nrd2008
K.C. Partlow, G.M. Lanza, S.A. Wickline, Biomaterials 29, 3367–3375 (2008). doi:10.1016/j.biomaterials.2008.04.030
S. Gupta, S.R. Indelicato, V. Jethwa, T. Kawabata, M. Kelley, A.R. Mire-Sluis, S.M. Richards, B. Rup, E. Shores, S.J. Swanson, E. Wakshull, J. Immunol. Methods 321, 1–18 (2007). doi:10.1016/j.jim.2006.12.004
J.H.J. Xu, P.V. Henstock, M.C. Dunn, A.R. Smith, J.R. Chabot, D. de Graaf, Cellular imaging predictions of clinical drug-induced liver injury. Toxicol. Sci 105, 97–105 (2008). doi:10.1093/toxsci/kfn109
H.M. Earl, L. Hiller, J.A. Dunn, S. Bathers, P. Harvey, A. Stanley, R.J. Grieve, R.K. Agrawal, I.N. Fernando, A.M. Brunt, K. McAdam, S. O’Reilly, D.W. Rea, D. Spooner, C.J. Pool, Brit. J. Cancer 99, 1226–1231 (2008). doi:10.1038/sj.bjc.6604674
C.L. Tseng, T.W. Wang, C.C. Dong, S.Y.H. Wu, T.H. Young, M.J. Shieh, P.J. Lou, F.H. Lin, Biomaterials 28, 3996–4005 (2007). doi:10.1016/j.biomaterials.2007.05.006
H.K. Patra, S. Banerjee, U. Chaudhuri, P. Lahiri, A.K. Dasgupta, Cell selective response to gold nanoparticles. Nanomedicine Nanotech. Biol. Med. 3, 111–119 (2007). doi:10.1016/j.nano.2007.03.005
F.K. Keter, S. Kanyanda, S.S.L. Lyantagaye, J. Darkwa, D.J.G. Rees, M. Meyer, Cancer Chemother. Pharmacol 63, 127–138 (2008). doi:10.1007/s00280-008-0721-y
P.C. Wu, C.H. Su, F.Y. Cheng, J.C. Weng, J.H. Chen, T.L. Tsai, C.S. Yeh, W.C. Su, J.R. Hwu, Y. Tzeng, D.B. Shieh, Bioconjug. Chem 19, 1972–1979 (2008a). doi:10.1021/bc800092w
P.C. Wu, W.S. Wang, Y.T. Huang, H.S. Sheu, Y.W. Lo, T.L. Tsai, D.B. Shieh, C.S. Yeh, Chem. Eur. J. 13, 3878–3885 (2007a). doi:10.1002/chem.200601372
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). doi:10.1002/bit.10143
H. Kaji, M. Nishizawa, T. Matsue, Lab Chip 3, 208–211 (2003). doi:10.1039/b304350a
A. Sin, K.C. Chin, M.F. Jamil, Y. Kostov, G. Rao, M.L. Shuler, Biotechnol. Prog 20, 338–345 (2004). doi:10.1021/bp034077d
S. Michael, S. Petronis, A.M. Jørgensen, C.B.V. Christensenc, M. Dufva, Lab Chip 6, 1045–1051 (2006). doi:10.1039/b603379b
A.M. Taylor, M. Blurton-Jones, S.W. Rhee, D.H. Cribbs, C.W. Cotman, N.L. Jeon, Nat. Methods 2, 599–605 (2005). doi:10.1038/nmeth777
D. Beebe, M. Wheeler, H. Zeringue, E. Walters, S. Raty, Microfluidic technology for assisted reproduction. Theriogenology 57, 125–135 (2002). doi:10.1016/S0093-691X(01)00662-8
S. Raty, E.M. Walters, J. Davis, H. Zeringue, D.J. Beebe, S.L. Rodriguez-Zax, M.B. Wheeler, Lab Chip 4, 186–190 (2004). doi:10.1039/b316437c
C.W. Huang, G.B. Lee, J. Micromech, Microeng 17, 1266–1274 (2007). doi:10.1088/0960-1317/17/7/008
M.H. Wu, J.P.G. Urban, Z. Cui, Z.F. Cui, Biomed. Microdevices 8, 331–340 (2006). doi:10.1007/s10544-006-9597-y
M. Sittinger, O. Schultz, G. Keyszer, W.W. Minuth, G.R. Burmester, Int. J. Artif. Organs 20, 57–62 (1997)
M.H. Wu, J.P.G. Urban, Z.F. Cui, Z. Cui, X. Xu, Biotechnol. Prog. 23, 430–434 (2007b). doi:10.1021/bp060024v
M.H. Wu, S.B. Huang, Z.F. Cui, Z. Cui, G.B. Lee, Sensor. Actuat. Biol. Chem. 129, 231–240 (2008b)
S.B. Huang, M.H. Wu, Z.F. Cui, Z. Cui, G.B. Lee, J. Micromech. Microeng 18, 045008 (12pp) (2008)
M.H. Wu, S.B. Huang, Z.F. Cui, Z. Cui, G.B. Lee, Biomed. Microdevices 10, 309–319 (2008c). doi:10.1007/s10544-007-9138-3
T.M. Hsieh, C.H. Luo, G.B. Lee, C.S. Liao, F.C. Huang, J. Med. Biol. Eng. 26, 43–49 (2006)
T.H. Huang, C.Y. Tsai, S.L. Chen, C.T. Kao, J. Biomed. Mater. Res. 63, 814–821 (2002). doi:10.1002/jbm.10412
R. Olinsji, P. Jaruga, M. Foksinski, K. Bialkowski, J. Tujakowski, Mol. Pharmacol. 52, 882–885 (1997)
X.Y. Wu, H.J. Liu, J.Q. Liu, K.N. Haley, J.A. Treadway, J.P. Larson, N.F. Ge, F. Peale, M.P. Bruchez, Nat. Biotechnol. 21, 41–46 (2003). doi:10.1038/nbt764
J.S. Pieper, T. Hafmans, J.H. Veerkamp, T.H. van Kuppevelt, Biomaterials 21, 581–593 (2000). doi:10.1016/S0142-9612(99)00222-7
M. Fraga, M. Lauxl, G.R. DosSantos, B. Zandona, C.D. Giuberti, M.C. de Oliveira, U.D. Matte, H.F. Teixeira, Pharmazie 63, 667–670 (2008)
P.J. Hung, P.J. Lee, P. Sabounchi, N. Aghdam, R. Lin, L.P. Lee, Lab Chip 5, 44–48 (2005). doi:10.1039/b410743h
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The authors would like to thank the National Science Council in Taiwan for financial support of this project.
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Hsieh, CC., Huang, SB., Wu, PC. et al. A microfluidic cell culture platform for real-time cellular imaging. Biomed Microdevices 11, 903–913 (2009). https://doi.org/10.1007/s10544-009-9307-7
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DOI: https://doi.org/10.1007/s10544-009-9307-7