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

Geeta Mehta

Associate Professor

mehtagee@umich.edu

3044 NCRC, Building 28

T: (734) 763-3957

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Geeta Mehta, Khamir Mehta, Dhruv Sud, Jonathan W Song, Tommaso Bersano-Begey, Nobuyuki Futai, Yun S Heo, Mary-Ann Mycek, Jennifer J Linderman, and Shuichi Takayama (2007)

BIOMEDICAL MICRODEVICES, 9(2):123-134.

Microfluidic bioreactors fabricated from highly gas-permeablepoly(dimethylsiloxane) (PDMS) materials have been observed, somewhatunexpectedly, to give rise to heterogeneous long term responses alongthe length of a perfused mammalian cell culture channel, reminiscent ofphysiologic tissue zonation that arises at least in part due to oxygengradients. To develop a more quantitative understanding and enablebetter control of the physical-chemical mechanisms underlying cellbiological events in such PDMS reactors, dissolved oxygen concentrationsin the channel system were quantified in real time using fluorescenceintensity and lifetime imaging of an oxygen sensitive dye, rutheniumtris(2,2'-dipyridyl) dichloride hexahydrate (RTDP). The data indicatethat despite oxygen diffusion through PDMS, uptake of oxygen by cellsinside the perfused PDMS microchannels induces an axial oxygenconcentration gradient, with lower levels recorded in downstreamregions. The oxygen concentration gradient generated by a balance ofcellular uptake, convective transport by media flow, and permeationthrough 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 cellularuptake can have important biological consequences. Results areconsistent with our mathematical model and give insight into theconditions under which flux of oxygen through PDMS into themicrochannels will or will not contribute significantly to oxygendelivery to cells and also provide a design tool to manipulate andcontrol oxygen for cell culture and device engineering. The combinationof computerized microfluidics, in situ oxygen sensing, and mathematicalmodels opens new windows for microphysiologic studies utilizing oxygengradients and low oxygen tensions.

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