Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture

Geeta Mehta, Khamir Mehta, Dhruv Sud, Jonathan W. Song, Tommaso Bersano-Begey, Nobuyuki Futai, Yun Seok Heo, Mary Ann Mycek, Jennifer J. Linderman, Shuichi Takayama

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

Microfluidic bioreactors fabricated from highly gas-permeable poly(dimethylsiloxane) (PDMS) materials have been observed, somewhat unexpectedly, to give rise to heterogeneous long term responses along the length of a perfused mammalian cell culture channel, reminiscent of physiologic tissue zonation that arises at least in part due to oxygen gradients. To develop a more quantitative understanding and enable better control of the physical-chemical mechanisms underlying cell biological events in such PDMS reactors, dissolved oxygen concentrations in the channel system were quantified in real time using fluorescence intensity and lifetime imaging of an oxygen sensitive dye, ruthenium tris(2,2'-dipyridyl) dichloride hexahydrate (RTDP). The data indicate that despite oxygen diffusion through PDMS, uptake of oxygen by cells inside the perfused PDMS microchannels induces an axial oxygen concentration gradient, with lower levels recorded in downstream regions. The oxygen concentration gradient generated by a balance of cellular uptake, convective transport by media flow, and permeation through PDMS in our devices ranged from 0.0003 (mg/l)/mm to 0.7 (mg/l)/mm. The existence of such steep gradients induced by cellular uptake can have important biological consequences. Results are consistent with our mathematical model and give insight into the conditions under which flux of oxygen through PDMS into the microchannels will or will not contribute significantly to oxygen delivery to cells and also provide a design tool to manipulate and control oxygen for cell culture and device engineering. The combination of computerized microfluidics, in situ oxygen sensing, and mathematical models opens new windows for microphysiologic studies utilizing oxygen gradients and low oxygen tensions.

Original languageEnglish
Pages (from-to)123-134
Number of pages12
JournalBiomedical Microdevices
Volume9
Issue number2
DOIs
Publication statusPublished - 2007 Apr 1
Externally publishedYes

Keywords

  • Fluorescence intensity
  • Fluorescence lifetime imaging microscopy (FLIM)
  • Microbioreactor
  • Microfluidics
  • Myoblast
  • Oxygen gradients
  • Oxygen sensing
  • PDMS
  • Rutheniumtris(2,2'-dipyridyl) dichloride hexahydrate (RTDP)

ASJC Scopus subject areas

  • Biomedical Engineering
  • Molecular Biology

Fingerprint Dive into the research topics of 'Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture'. Together they form a unique fingerprint.

  • Cite this

    Mehta, G., Mehta, K., Sud, D., Song, J. W., Bersano-Begey, T., Futai, N., Heo, Y. S., Mycek, M. A., Linderman, J. J., & Takayama, S. (2007). Quantitative measurement and control of oxygen levels in microfluidic poly(dimethylsiloxane) bioreactors during cell culture. Biomedical Microdevices, 9(2), 123-134. https://doi.org/10.1007/s10544-006-9005-7