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Biomicrofluidics / Volume 5 / Issue 2 / REGULAR ARTICLES

Biomicrofluidics 5, 024110 (2011); http://dx.doi.org/10.1063/1.3596530 (10 pages)

Continuously perfused microbubble array for 3D tumor spheroid model

Sivaprakash Agastin1, Ut-Binh T. Giang2, Yue Geng1, Lisa A. DeLouise2,3, and Michael R. King1

1Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA
2Department of Biomedical Engineering, University of Rochester, Rochester, New York 14642, USA
3Department of Dermatology, University of Rochester, Rochester, New York 14642, USA

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(Received 15 February 2011; accepted 9 May 2011; published online 3 June 2011; publisher error corrected 6 June 2011)

Multi-cellular tumor spheroids (MCTSs) have been established as a 3D physiologically relevant tumor model for drug testing in cancer research. However, it is difficult to control the MCTS testing parameters and the entire process is time-consuming and expensive. To overcome these limitations, we developed a simple microfluidic system using polydimethylsiloxane (PDMS) microbubbles to culture tumor spheroids under physiological flow. The flow characteristics such as streamline directions, shear stress profile, and velocity profile inside the microfluidic system were first examined computationally using a COMSOL simulation. Colo205 tumor spheroids were created by a modified hanging drop method and maintained inside PDMS microbubble cavities in perfusion culture. Cell viability inside the microbubbles was examined by live cell staining and confocal imaging. E-selectin mediated cell sorting of Colo205 and MDA-MB-231 cell lines on functionalized microbubble and PDMS surfaces was achieved. Finally, to validate this microfluidic system for drug screening purposes, the toxicity of the anti-cancer drug, doxorubicin, on Colo205 cells in spheroids was tested and compared to cells in 2D culture. Colo205 spheroids cultured in flow showed a threefold increase in resistance to doxorubicin compared to Colo205 monolayer cells cultured under static conditions, consistent with the resistance observed previously in other MCTS models. The advantages presented by our microfluidic system, such as the ability to control the size uniformity of the spheroids and to perform real-time imaging on cells in the growth platform, show potential for high throughput drug screening development.

© 2011 American Institute of Physics

Article Outline

  1. INTRODUCTION
  2. MATERIALS AND METHODS
    1. Cell culture
    2. Colo205 spheroids
    3. COMSOL Simulation
    4. Colo205 cell preparation for cell capture experiments
    5. PDMS microbubbles
    6. Perfusion chamber
    7. PDMS surface preparation
    8. Cell capture inside PDMS microbubbles
    9. Cell staining and doxorubicin toxicity assay
    10. Imaging and data analysis
  3. RESULTS AND DISCUSSION
  4. CONCLUSIONS

EDITORIALLY RELATED

  1. Publisher's Note: “Continuously perfused microbubble array for 3D tumor spheroid model” [Biomicrofluidics 5, 024110 (2011)]
    Sivaprakash Agastin et al.
    Biomicrofluidics 5, 039901 (2011)BIOMGB000005000003039901000001

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KEYWORDS and PACS

Keywords

biomedical imaging, bioMEMS, bubbles, cancer, cellular biophysics, drugs, microfluidics, monolayers, physiological models, polymers, tumours

PACS

  • 87.57.-s

    Medical imaging

  • 87.85.Ox

    Biomedical instrumentation and transducers, including micro-electro-mechanical systems (MEMS)

ARTICLE DATA

Digital Object Identifier
http://dx.doi.org/10.1063/1.3596530

PUBLICATION DATA

ISSN

1932-1058 (online)

Publisher

$abstract.society.value is a Member of CrossRef American Institute of Physics

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