Finite element analysis of oxygen transport in microfluidic cell culture devices with varying channel architectures, perfusion rates, and materials

Zahorodny-Burke, M.; Nearingburg, B.; Elias, Anastasia L.

doi:10.1016/j.ces.2011.09.007

Cited by 25 publications

(30 citation statements)

References 49 publications

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“…Considering a hepatocyte-compatible wall shear stress of τ w = 15 μPa on the surface of the hydrogel construct, the v in was fixed at 7.1 × 10 −7 m/s and 7.1 × 10 −6 m/s, respectively, for the micro-and the milli-fluidic systems. These velocities are consistent with those typically reported for micro-fluidic cell culture devices [42]. For the MCmB model, the v in was set to 3.82 × 10 −3 m/s (corresponding to 180 μL/min inflow), on the basis of previous experiments with this bioreactor [31,[62][63][64][65][66].…”

Section: Model Implementationsupporting

confidence: 60%

“…According to previous considerations (Section 2), the smallest physiologically relevant in vitro model is a 0.2 × 20 × 0.2 mm 3 parallelepiped containing 7 × 10 7 cells/mL (i.e., 10 functional units in terms of cell number and 1/10 of native cell density). Thus, in both systems the bottom area of the fluid channel was considered equal to the cell construct surface (i.e., 0.2 × 20 mm 2 ), while its thickness (h) was taken as 0.2 mm or 2 mm, respectively for the micro-and milli-scaled fluidic channels ( Figure 3) [30,42,43]. Second, as a case study we considered a real bioreactor, the Multi-Compartmental modular Bioreactor (MCmB, Figure 4).…”

Section: Modelled Configurationsmentioning

confidence: 99%

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Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

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Abstract:In this paper, we discuss the basic design requirements for the development of physiologically meaningful in vitro systems comprising cells, scaffolds and bioreactors, through a bottom up approach. Very simple micro-and milli-fluidic geometries are first used to illustrate the concepts, followed by a real device case-study. At each step, the fluidic and mass transport parameters in biological tissue design are considered, starting from basic questions such as the minimum number of cells and cell density required to represent a physiological system and the conditions necessary to ensure an adequate nutrient supply to tissues. At the next level, we consider the use of three-dimensional scaffolds, which are employed both for regenerative medicine applications and for the study of cells in environments which better recapitulate the physiological milieu. Here, the driving need is the rate of oxygen supply which must be maintained at an appropriate level to ensure cell viability throughout the thickness of a scaffold. Scaffold and bioreactor design are both critical in defining the oxygen profile in a cell construct and are considered together. We also discuss the oxygen-shear stress trade-off by considering the levels of mechanical stress required for hepatocytes, which are the limiting cell type in a multi-organ model. Similar considerations are also made for glucose consumption in cell constructs. Finally, the allometric approach for generating multi-tissue systemic models using bioreactors is described.

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Section: Model Implementationsupporting

confidence: 60%

Section: Modelled Configurationsmentioning

confidence: 99%

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

2014

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“…In these microfluidic culture devices, poly (dimethylsiloxane) (PDMS) has become the most popular material because of its simple fabrication process, low cost, optical transparency, biocompatibility and gas permeability (Duffy et al, 1998;Gao et al, 2012). Using gas permeability properties, several PDMSbased microfluidic devices have been developed to generate desired oxygen (Adler et al, 2010;Chen et al, 2011;Inamdar et al, 2011;Polinkovsky et al, 2009;Shiku et al, 2006;Skolimowski et al, 2010;Zahorodny-Burke et al, 2011) and carbon dioxide (CO 2 ) (Forry and Locascio, 2011;Polinkovsky et al, 2009;Takano et al, 2012) concentrations for cell cultures.…”

Section: Introductionmentioning

confidence: 99%

Modeling carbon dioxide transport in PDMS-based microfluidic cell culture devices

Mäki

Peltokangas

Kreutzer

et al. 2015

Chemical Engineering Science

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“…microfluidic devices for establishing hypoxia in cell cultures [12]. Many of these studies apply mathematical modelling to verify that they are correctly maintaining their target O 2 levels [13–15, 17, 18]. …”

Section: Introductionmentioning

confidence: 99%

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

et al. 2016

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Red blood cells play a crucial role in the local regulation of oxygen supply in the microcirculation through the oxygen dependent release of ATP. Since red blood cells serve as an oxygen sensor for the circulatory system, the dynamics of ATP release determine the effectiveness of red blood cells to relate the oxygen levels to the vessels. Previous work has focused on the feasibility of developing a microfluidic system to measure the dynamics of ATP release. The objective was to determine if a steep oxygen gradient could be developed in the channel to cause a rapid decrease in hemoglobin oxygen saturation in order to measure the corresponding levels of ATP released from the red blood cells. In the present study, oxygen transport simulations were used to optimize the geometric design parameters for a similar system which is easier to fabricate. The system is composed of a microfluidic device stacked on top of a large, gas impermeable flow channel with a hole to allow gas exchange. The microfluidic device is fabricated using soft lithography in polydimethyl-siloxane, an oxygen permeable material. Our objective is twofold: (1) optimize the parameters of our system and (2) develop a method to assess the oxygen distribution in complex 3D microfluidic device geometries. 3D simulations of oxygen transport were performed to simulate oxygen distribution throughout the device. The simulations demonstrate that microfluidic device geometry plays a critical role in molecule exchange, for instance, changing the orientation of the short wide microfluidic channel results in a 97.17% increase in oxygen exchange. Since microfluidic devices have become a more prominent tool in biological studies, understanding the transport of oxygen and other biological molecules in microfluidic devices is critical for maintaining a physiologically relevant environment. We have also demonstrated a method to assess oxygen levels in geometrically complex microfluidic devices.

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Finite element analysis of oxygen transport in microfluidic cell culture devices with varying channel architectures, perfusion rates, and materials

Cited by 25 publications

References 49 publications

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Design Criteria for Generating Physiologically Relevant In Vitro Models in Bioreactors

Modeling carbon dioxide transport in PDMS-based microfluidic cell culture devices

Finite Element Model of Oxygen Transport for the Design of Geometrically Complex Microfluidic Devices Used in Biological Studies

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