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Dixon AR, Rajan S, Kuo CH, et al. Microfluidic device capable of medium recirculation for non-adherent cell culture. Biomicrofluidics. 2014;8(1):016503doi: 10.1063/1.4865855.
Dixon, A. R., Rajan, S., Kuo, C. H., Bersano, T., Wold, R., Futai, N., Takayama, S., & Mehta, G. (2014). Microfluidic device capable of medium recirculation for non-adherent cell culture. Biomicrofluidics, 8(1), 016503. https://doi.org/10.1063/1.4865855
Dixon, Angela R, et al. "Microfluidic device capable of medium recirculation for non-adherent cell culture." Biomicrofluidics vol. 8,1 (2014): 016503. doi: https://doi.org/10.1063/1.4865855
Dixon AR, Rajan S, Kuo CH, Bersano T, Wold R, Futai N, Takayama S, Mehta G. Microfluidic device capable of medium recirculation for non-adherent cell culture. Biomicrofluidics. 2014 Feb 25;8(1):016503. doi: 10.1063/1.4865855. eCollection 2014 Jan. PMID: 24753733; PMCID: PMC3977789.
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Biomicrofluidics. 2014 Feb 25;8(1):016503. doi: 10.1063/1.4865855. eCollection 2014 Jan.

Microfluidic device capable of medium recirculation for non-adherent cell culture.

Biomicrofluidics

Angela R Dixon, Shrinidhi Rajan, Chuan-Hsien Kuo, Tom Bersano, Rachel Wold, Nobuyuki Futai, Shuichi Takayama, Geeta Mehta

Affiliations

  1. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
  2. Department of Mechanical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA ; Mobility and Thermal Management Department, General Dynamics Land Systems, Sterling Heights, Michigan 48310, USA.
  3. Google, Inc., 1600 Amphitheatre Parkway Mountain View, California 94043, USA ; University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109, USA.
  4. Department of Mechanical Engineering, Shibaura Institute of Technology, 3-5-1 Toyosu, Koto-ku, Tokyo 135-8548, Japan.
  5. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA ; Department of Macromolecular Science and Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
  6. Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA ; Department of Materials Science and Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.

PMID: 24753733 PMCID: PMC3977789 DOI: 10.1063/1.4865855

Abstract

We present a microfluidic device designed for maintenance and culture of non-adherent mammalian cells, which enables both recirculation and refreshing of medium, as well as easy harvesting of cells from the device. We demonstrate fabrication of a novel microfluidic device utilizing Braille perfusion for peristaltic fluid flow to enable switching between recirculation and refresh flow modes. Utilizing fluid flow simulations and the human promyelocytic leukemia cell line, HL-60, non-adherent cells, we demonstrate the utility of this RECIR-REFRESH device. With computer simulations, we profiled fluid flow and concentration gradients of autocrine factors and found that the geometry of the cell culture well plays a key role in cell entrapping and retaining autocrine and soluble factors. We subjected HL-60 cells, in the device, to a treatment regimen of 1.25% dimethylsulfoxide, every other day, to provoke differentiation and measured subsequent expression of CD11b on day 2 and day 4 and tumor necrosis factor-alpha (TNF-α) on day 4. Our findings display perfusion sensitive CD11b expression, but not TNF-α build-up, by day 4 of culture, with a 1:1 ratio of recirculation to refresh flow yielding the greatest increase in CD11b levels. RECIR-REFRESH facilitates programmable levels of cell differentiation in a HL-60 non-adherent cell population and can be expanded to other types of non-adherent cells such as hematopoietic stem cells.

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