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A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors.

Publication ,  Journal Article
Elliott, NT; Yuan, F
Published in: Biotechnology and Bioengineering
May 2012

Three-dimensional (3D) tumor models have been established in various microfluidic systems for drug delivery and resistance studies in vitro. However, one of the main drawbacks of these models is non-uniform distribution of cells, leaving regions with very low cell density within the 3D structures. As a result, molecular diffusion in the cell compartments is faster than that observed in solid tumors. To solve this problem, we developed a new technique for preparation of 3D tumor models in vitro. It was based on a microfluidic device containing three parallel channels separated by narrowly spaced posts. Tumor cells were loaded into the central channel at high density. To test the system, B16.F10 melanoma cells were perfusion-cultured overnight and the resulting 3D structure was characterized in terms of viability, density, and morphology of cells as well as transport properties of small fluorescent molecules. Immediately upon loading of tumor cells, the cell density was comparable to those observed in B16.F10 tumor tissues in vivo; and the viability of tumor cells was maintained through the overnight culture. The tumor model displayed low extracellular space and high resistance to diffusion of small molecules. For membrane-permeant molecules (e.g., Hoechst 33342), the rate of interstitial penetration was extremely slow, compared to membrane-impermeant molecules (e.g., sodium fluorescein). This versatile tumor model could be applied to in vitro studies of transport and cellular uptake of drugs and genes.

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Published In

Biotechnology and Bioengineering

DOI

EISSN

1097-0290

ISSN

0006-3592

Publication Date

May 2012

Volume

109

Issue

5

Start / End Page

1326 / 1335

Related Subject Headings

  • Plasmacytoma
  • Organ Culture Techniques
  • Models, Theoretical
  • Microfluidics
  • Mice
  • Cell Line, Tumor
  • Biotechnology
  • Antineoplastic Agents
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Elliott, N. T., & Yuan, F. (2012). A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors. Biotechnology and Bioengineering, 109(5), 1326–1335. https://doi.org/10.1002/bit.24397
Elliott, Nelita T., and Fan Yuan. “A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors.Biotechnology and Bioengineering 109, no. 5 (May 2012): 1326–35. https://doi.org/10.1002/bit.24397.
Elliott NT, Yuan F. A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors. Biotechnology and Bioengineering. 2012 May;109(5):1326–35.
Elliott, Nelita T., and Fan Yuan. “A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors.Biotechnology and Bioengineering, vol. 109, no. 5, May 2012, pp. 1326–35. Epmc, doi:10.1002/bit.24397.
Elliott NT, Yuan F. A microfluidic system for investigation of extravascular transport and cellular uptake of drugs in tumors. Biotechnology and Bioengineering. 2012 May;109(5):1326–1335.
Journal cover image

Published In

Biotechnology and Bioengineering

DOI

EISSN

1097-0290

ISSN

0006-3592

Publication Date

May 2012

Volume

109

Issue

5

Start / End Page

1326 / 1335

Related Subject Headings

  • Plasmacytoma
  • Organ Culture Techniques
  • Models, Theoretical
  • Microfluidics
  • Mice
  • Cell Line, Tumor
  • Biotechnology
  • Antineoplastic Agents
  • Animals