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Timescale analysis for estimating upper limit perfusion rate in a microfluidic perfusion cell culture platform

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Abstract

Proliferation characteristics of CHO-K1 cells were investigated under a variety of medium perfusion rate conditions in a microfluidic perfusion cell culture platform. Five microcavities of \(800\,\upmu \hbox {m}~(w)\,\times \,800\,\upmu \hbox {m}~(l)\,\times \,400\,\upmu \hbox {m}~(h)\) were adopted in order to minimize or isolate the shear effects on cell surfaces. Microchannels of \(800\,\upmu \hbox {m}~(w)\,\times \,3.5\,\hbox {mm}~(l)\,\times \,100\,\upmu \hbox {m}~(h)\) serially connecting these microcavities created flow contractions and expansions repeatedly, resulting in two different diffusion and convection timescales through the platform. Average shear stresses on the bottom of microcavity were both numerically and analytically estimated, and medium flow was operated at rates where shear stress is below \(\sim\)2 mPa. Proliferation rates of CHO-K1 cells were investigated based both on population groups derived from the number of initially seeded cells and on the microcavity locations. Population groups showed minimal influences on proliferation rates, while proliferation rates increased clearly with medium perfusion rates. Strong effects of microcavity locations were observed on proliferation at \(\hbox {Pe}\,\ge \,45\). Such effects were analyzed by investigating the relationships of reaction, diffusion, and convection timescales associated with perfusion conditions. The ratio of diffusion timescale and convection timescale was suggested as a guideline to estimate the upper limit of perfusion rate in microfluidic perfusion cell culture platform.

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Acknowledgments

This work was supported by the KIST Institutional Program (2E24700) and by Convergence Technology Development Program (S2096502) of Small and Medium Business Administration of Korea. S. Chung was supported by NRF (2012-022481) and Human Energy, Republic of Korea (20124010203250).

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Authors and Affiliations

  1. Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea

    Joon-Ho Maeng, Hyun-Joon Shin, Sehoon Kim & Sangyoup Lee

  2. Department of Mechanical Engineering, Korea University, Seoul, 136-701, Republic of Korea

    Hyo Eun Jeong & Seok Chung

  3. Department of Biomedical Engineering, University of Science and Technology (UST), Daejeon, 305-350, Republic of Korea

    Hyun-Joon Shin, Sehoon Kim & Sangyoup Lee

  4. School of Mechanical and Automotive Engineering, Gangneung-Wonju National University, Wonju, 220-711, Republic of Korea

    Jong-Chul Lee

  5. Graduate School of Mechanical Engineering, Sungkyunkwan University, Suwon, 440-746, Republic of Korea

    Jaeyoung Lee

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  1. Joon-Ho Maeng
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  2. Hyo Eun Jeong
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  5. Jong-Chul Lee
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Correspondence to Sangyoup Lee.

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Maeng, JH., Jeong, H.E., Shin, HJ. et al. Timescale analysis for estimating upper limit perfusion rate in a microfluidic perfusion cell culture platform. Microfluid Nanofluid 19, 777–786 (2015). https://doi.org/10.1007/s10404-015-1602-4

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  • DOI: https://doi.org/10.1007/s10404-015-1602-4

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