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Fluid Dynamics Analysis of a Novel Micropatterned Cell Bioreactor

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Abstract

Although flow-based bioreactor has been widely used to provide sufficient mass transportation and nutrient supply for cell proliferation, differentiation, and apoptosis, the underlying mechanism of cell responses to applied flow at single cell level remains unclear. This study has developed a novel bioreactor that combines flow bioreactor with microfabrication technique to isolate individual cells onto micropatterned substrate. A mechanical model has also been developed to quantify the flow field or the microenvironment around the single cell; flow dynamics has been analyzed on five geometrically different patterns of circle-, cube-, 1:2 ellipse-, 1:3 ellipse-, and rectangle-shaped “virtual cells.” The results of this study have demonstrated that the flow field is highly pattern dependent, and all the hydrodynamic development length, cell spacing, and orientation of inlet velocity vector are crucial for maintaining a fully developed flow. This study has provided a theoretical basis for optimizing the design of micropatterned flow bioreactor and a novel approach to understand the cell mechanotransduction and cell–surface interaction at single cell level.

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Abbreviations

a, b, h:

Length, width, height of an isolated cell

ATR:

Active test region

(c − a)/a = (d − b)/b :

Spacing ratio

c, d:

Length, width of an unit

D :

Hydrodynamic diameter (=2WH/(W + H))

F b :

Body force per unit mass

L, W, H:

Length, width, height of a flow chamber

Linlet, Loutlet, Lwall:

Inlet, outlet, wall length of a flow chamber

Linlet/D, Loutlet/D, Lwall/D:

Non-dimensional hydrodynamic development inlet, outlet, wall length in a micropatterned flow chamber

\( L^{\prime}_{\text{inlet}} \), \( L^{\prime}_{\text{outlet}} \), \( L^{\prime}_{\text{wall}} \):

Applied inlet, outlet, wall length in a flow chamber when the computation is need

p :

Pressure of flow field

p t :

Relative pressure

Q :

Flow flux of flowing fluid

Re :

Reynolds number

u :

Velocity vector of flowing fluid

α, β, γ:

Non-dimensional hydrodynamic development lengths of inlet, outlet, wall in a cell seeded flow chamber

Θ, ∇:

Substantive derivative, vector differential operator

μ :

Dynamic viscosity of flowing fluid

ρ :

Mass density of flowing fluid

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Acknowledgments

The authors are grateful to Xin Wang, Yunfeng Wu, and Yabin Zhai for computational assistance. This study was supported by the following grants: the Natural Science Foundation of China, #30730032 and #30870606; Knowledge Innovation Program of CAS, #KJCX2-YW-L08; the National Key Basic Research Foundation of China, #2006CB910303; and the National High Technology Research and Development Program of China, #2007AA02Z306.

Conflict of interest statement

No conflict of interested is assigned to the manuscript.

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Authors and Affiliations

  1. Department of Mechanics, Tianjin University, Tianjin, 300072, People’s Republic of China

    Yuhong Cui

  2. Key Laboratory of Microgravity, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Bo Huo, Shujin Sun, Fan Yang, Yuxin Gao & Mian Long

  3. National Microgravity Laboratory, Beijing, 100190, People’s Republic of China

    Bo Huo, Shujin Sun, Fan Yang, Yuxin Gao & Mian Long

  4. Center for Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, People’s Republic of China

    Bo Huo, Shujin Sun, Fan Yang, Yuxin Gao & Mian Long

  5. Bioengineering College, Chongqing University, Chongqing, 400030, People’s Republic of China

    Jun Pan

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  1. Yuhong Cui
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Correspondence to Mian Long.

Additional information

Associate Editor Tingrui Pan oversaw the review of this article.

Yuhong Cui and Bo Huo contributed equally to this work.

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Cui, Y., Huo, B., Sun, S. et al. Fluid Dynamics Analysis of a Novel Micropatterned Cell Bioreactor. Ann Biomed Eng 39, 1592–1605 (2011). https://doi.org/10.1007/s10439-011-0250-4

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  • DOI: https://doi.org/10.1007/s10439-011-0250-4

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