Skip to main content

Advertisement

Log in

Alginate-based microfluidic system for tumor spheroid formation and anticancer agent screening

  • Published:
Biomedical Microdevices Aims and scope Submit manuscript

Abstract

We demonstrate a microfluidic system for long-term tumor cell culture and drug testing. Three-dimensional cell culture is critical in characterizing anticancer treatments since it may provide a better model than monolayer culture of tumor cells. Breast tumor cells were encapsulated within alginate which was gelled in situ within the microchannels. Tumor spheroid formation was observed several days after cell seeding, and various concentrations of doxorubicin were applied to the encapsulated cell aggregates. Drug effects on cell viability and proliferation were measured. In future, hydrogel-based microfluidic devices can comprise part of systems which replace labor intensive screening platforms currently implemented in the laboratory, and they address a need for improving preclinical testing of cancer cell sensitivity to anti-cancer drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • A. Abbott, Nature 424, 870–872 (2003)

    Article  Google Scholar 

  • D.R. Albrecht, G.H. Underhill, T.B. Wassermann, R.L. Sah, S.N. Bhatia, Nat. Methods 3, 369–375 (2006)

    Article  Google Scholar 

  • G. Aubel-Sadron, D. Londos-Gagliardi, Biochimie 66, 333–352 (1984)

    Article  Google Scholar 

  • K. Bhadriraju, C.S. Chen, Drug Discov. Today 7, 612–620 (2002)

    Article  Google Scholar 

  • M.J. Bissell, D. Radisky, Nat. Rev. Cancer 1, 46–54 (2001)

    Article  Google Scholar 

  • T. Braschler, R. Johann, M. Heule, L. Metref, P. Renaud, Lab Chip 5, 553–559 (2005)

    Article  Google Scholar 

  • S.P. Desai, D.M. Freeman, J. Voldman, Lab Chip 9, 1631–1637 (2009)

    Article  Google Scholar 

  • B. Desoize, J.-C. Jardillier, Crit. Rev. Oncol. Hematol. 36, 193–207 (2000)

    Article  Google Scholar 

  • W.H. Dragowska, C. Warburton, D.T.T. Yapp, A.I. Minchinton, Y. Hu, D.N. Waterhouse, K. Gelmon, K. Skov, J. Woo, D. Masin, L.A. Huxham, A.H. Kyle, M.B. Bally, Mol. Cancer Res. 2, 606–619 (2004)

    Google Scholar 

  • Y. Du, J. Shim, M. Vidula, M.J. Hancock, E. Lo, B.G. Chung, J.T. Borenstein, M. Khabiry, D.M. Cropek, A. Khademhosseini, Lab Chip 9, 761–767 (2009)

    Article  Google Scholar 

  • J. Friedrich, C. Seidel, R. Ebner, L.A. Kunz-Schughart, Nat. Protoc. 4, 309–324 (2009)

    Article  Google Scholar 

  • J. García-Alonso, G.M. Greenway, J.D. Hardege, S.J. Haswell, Biosens. Bioelectron. 24, 1508–1511 (2009)

    Article  Google Scholar 

  • H. Goldie, M. Dingman Felix, Cancer Res. 11, 73–80 (1951)

    Google Scholar 

  • R. Johann, Anal. Bioanal. Chem. 385, 408–412 (2006)

    Article  Google Scholar 

  • R.M. Johann, P. Renaud, Biointerphases 2, 73–79 (2007)

    Article  Google Scholar 

  • J. Kalra, C. Warburton, K. Fang, L. Edwards, T. Daynard, D. Waterhouse, W. Dragowska, B. Sutherland, S. Dedhar, K. Gelmon, M. Bally, Breast Cancer Res. 11, R25 (2009)

    Article  Google Scholar 

  • T.M. Keenan, A. Folch, Lab Chip 8, 34–57 (2008)

    Article  Google Scholar 

  • M. Khalil, A. Shariat-Panahi, R. Tootle, T. Ryder, P. McCloskey, E. Roberts, H. Hodgson, C. Selden, J. Hepatol. 34, 68–77 (2001)

    Article  Google Scholar 

  • G. Klein, E. Klein, Ann. N. Y. Acad. Sci. 63, 640–661 (1956)

    Article  Google Scholar 

  • L.A. Kunz-Schughart, Cell Biol. Int. 23, 157–161 (1999)

    Article  Google Scholar 

  • L.A. Kunz-Schughart, J.P. Freyer, F. Hofstaedter, R. Ebner, J. Biomol. Screen. 9, 273–285 (2004)

    Article  Google Scholar 

  • E. Leclerc, Y. Sakai, T. Fujii, Biomed. Microdevices 5, 109–114 (2003)

    Article  Google Scholar 

  • P.J. Lee, T.A. Gaige, N. Ghorashian, P.J. Hung, Biotechnol. Prog. 23, 946–951 (2007)

    Google Scholar 

  • F. Leonessa, D. Green, T. Licht, A. Wright, K. Wingate-Legette, J. Lippman, M.M. Gottesman, R. Clarke, Br. J. Cancer 73, 154–161 (1996)

    Google Scholar 

  • R.-Z. Lin, H.-Y. Chang, Biotechnol. J. 3, 1172–1184 (2008)

    Article  Google Scholar 

  • Y. Ling, J. Rubin, Y. Deng, C. Huang, U. Demirci, J.M. Karp, A. Khademhosseini, Lab Chip 7, 756–762 (2007)

    Article  Google Scholar 

  • B. Ma, G. Zhang, J. Qin, B. Lin, Lab Chip 9, 232–238 (2009)

    Article  Google Scholar 

  • G. Malich, B. Markovic, C. Winder, Toxicology 124, 179–192 (1997)

    Article  Google Scholar 

  • W.F. McLimans, E.V. Davis, F.L. Glover, G.W. Rake, J. Immunol. 79, 428–433 (1957)

    Google Scholar 

  • I. Meyvantsson, D.J. Beebe, 2008. Annu. Rev. Anal. Chem. 1, 423–449 (2008)

    Article  Google Scholar 

  • W. Mueller-Klieser, J. Cancer Res. Clin. Oncol. 113, 101–122 (1987)

    Article  Google Scholar 

  • J.A. Nagy, M.S. Meyers, E.M. Masse, K.T. Herzberg, H.F. Dvorak, Cancer Res. 55, 360–368 (1995)

    Google Scholar 

  • C.P. Ng, S.H. Pun, Biotechnol. Bioeng. 99, 1490–1501 (2008)

    Article  Google Scholar 

  • P.L. Olive, R.E. Durand, Cancer Metastasis Rev. 13, 121–138 (1994)

    Article  Google Scholar 

  • M. Rajaonarivony, C. Vauthier, G. Couarraze, F. Puisieux, P. Couvreur, J. Pharm. Sci. 82, 912–917 (1993)

    Article  Google Scholar 

  • K.J. Regehr, M. Domenech, J.T. Koepsel, K.C. Carver, S.J. Ellison-Zelski, W.L. Murphy, L.A. Schuler, E.T. Alarid, D.J. Beebe, Lab Chip 9, 2132–2139 (2009)

    Article  Google Scholar 

  • J.A. Rowley, G. Madlambayan, D.J. Mooney, Biomaterials 20, 45–53 (1999)

    Article  Google Scholar 

  • M.T. Santini, G. Rainaldi, P.L. Indovina, Crit. Rev. Oncol. Hematol. 36, 75–87 (2000)

    Article  Google Scholar 

  • A. Shilpa, S.S. Agrawal, A.R. Ray, Polym. Rev. 43, 187–221 (2003)

    Article  Google Scholar 

  • J.H. Sung, M.L. Shuler, Lab Chip 9, 1385–1394 (2009)

    Article  Google Scholar 

  • R. Sutherland, J. McCredi, W. Inch, J. Natl Cancer Inst. 46, 113–120 (1971)

    Google Scholar 

  • R.M. Sutherland, H.A. Eddy, B. Bareham, K. Reich, D. Vanantwerp, Int. J. Radiat. Oncol. Biol. Phys. 5, 1225–1230 (1979)

    Google Scholar 

  • A. Tirella, M. Marano, F. Vozzi, A. Ahluwalia, Toxicol. In Vitro 22, 1957–1964 (2008)

    Article  Google Scholar 

  • M.W. Toepke, D.J. Beebe, Lab Chip 6, 1484–1486 (2006)

    Article  Google Scholar 

  • Y.-C. Toh, C. Zhang, J. Zhang, Y.M. Khong, S. Chang, V.D. Samper, D.V. Noort, D.W. Hutmacher, H. Yu, Lab Chip 7, 302–309 (2007)

    Article  Google Scholar 

  • Y.-C. Toh, T.C. Lim, D. Tai, G. Xiao, D.V. Noort, H. Yu, Lab Chip 9, 2026–2035 (2009)

    Article  Google Scholar 

  • H.H. Tønnesen, J. Karlsen, Drug Dev. Ind. Pharm. 28, 621–630 (2002)

    Article  Google Scholar 

  • T. Visted, R. Bjerkvig, P.O. Enger, Neuro-oncology 3, 201–210 (2001)

    Article  Google Scholar 

  • V. Vogel, G. Baneyx, Annu. Rev. Biomed. Eng. 5, 441–463 (2003)

    Article  Google Scholar 

  • G.M. Whitesides, E. Ostuni, S. Takayama, X. Jiang, D.E. Ingber, Annu. Rev. Biomed. Eng. 3, 335–373 (2001)

    Article  Google Scholar 

  • V.L. Workman, S.B. Dunnett, P. Kille, D.D. Palmer, Macromol. Rapid Commun. 29, 165–170 (2008)

    Article  Google Scholar 

  • L. Wu, D. Di Carlo, L. Lee, Biomed. Microdevices 10, 197–202 (2008)

    Article  Google Scholar 

  • X. Zhang, W. Wang, W. Yu, Y. Xie, X. Zhang, Y. Zhang, X. Ma, Biotechnol. Prog. 21, 1289–1296 (2005)

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded in part by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Canadian Breast Cancer Research Alliance (CBCRA), and the Canada Foundation for Innovation (CFI). We would like to thank John Jackson for helpful discussions. Dr. Marcel Bally generously provided the LCC6/Her-2 breast tumor cells.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Karen C. Cheung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, M.C.W., Gupta, M. & Cheung, K.C. Alginate-based microfluidic system for tumor spheroid formation and anticancer agent screening. Biomed Microdevices 12, 647–654 (2010). https://doi.org/10.1007/s10544-010-9417-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10544-010-9417-2

Keywords

Navigation