Design and fabrication of micro/bio chip for in vitro fabrication of toroidal cellular aggregates

Chumtong, Puwanan; Kojima, Masaru; Horade, Mitsuhiro; Ohara, Kenichi; Kamiyama, Kazuto; Mae, Yasushi; Akiyama, Yoshikatsu; Yamato, Masayuki; Arai, Tatsuo

doi:10.1109/icma.2014.6885668

Cited by 3 publications

(4 citation statements)

References 31 publications

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“…They demonstrated that cell viability for toroid was higher than that of the spheroid. Chumtong et al [ 14 ] used a similar system to produce the toroid. Their system had an array of deformable scaffolds coated by an elastic membrane with a central micropillar.…”

Section: Introductionmentioning

confidence: 99%

Numerical Simulation of the Behavior of Toroidal and Spheroidal Multicellular Aggregates in Microfluidic Devices with Microwell and U-Shaped Barrier

et al. 2017

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A microfluidic system provides an excellent platform for cellular studies. Most importantly, a three-dimensional (3D) cell culture model reconstructs more accurately the in vivo microenvironment of tissue. Accordingly, microfluidic 3D cell culture devices could be ideal candidates for in vitro cell culture platforms. In this paper, two types of 3D cellular aggregates, i.e., toroid and spheroid, are numerically studied. The studies are carried out for microfluidic systems containing U-shaped barrier as well as microwell structure. For the first time, we obtain oxygen and glucose concentration distributions inside a toroid aggregate as well as the shear stress on its surface and compare its performance with a spheroid aggregate of the same volume. In particular, we obtain the oxygen concentration distributions in three areas, namely, oxygen-permeable layer, multicellular aggregates and culture medium. Further, glucose concentration distributions in two regions of multicellular aggregates and culture medium are investigated. The results show that the levels of oxygen and glucose in the system containing U-shaped barriers are far more than those in the system containing microwells. Therefore, to achieve high levels of oxygen and nutrients, a system with U-shaped barriers is more suited than the conventional traps, but the choice between toroid and spheroid depends on their volume and orientation. The results indicate that higher oxygen and glucose concentrations can be achieved in spheroid with a small volume as well as in horizontal toroid with a large volume. The vertical toroid has the highest levels of oxygen and glucose concentration while the surface shear stress on its surface is also maximum. These findings can be used as guidelines for designing an optimum 3D microfluidic bioreactor based on the desired levels of oxygen, glucose and shear stress distributions.

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Section: Introductionmentioning

confidence: 99%

Numerical Simulation of the Behavior of Toroidal and Spheroidal Multicellular Aggregates in Microfluidic Devices with Microwell and U-Shaped Barrier

et al. 2017

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“…In order to achieve this, one can assume u s = 0. However, this still leaves the tangential fluid stress balance mentioned above in Equation (15). This makes the system inconsistent as the tangential fluid stress has been already taken care of by the Beavers-Joseph condition.…”

Section: Hydrodynamic Boundary Conditionsmentioning

confidence: 99%

“…so that the limit u s = 0 and = 0 removes the additional condition. On the other hand, we must have = 1 for deformable porous medium so that we retain the required tangential stress balance as in Equation (15). Moreover, continuity of normal stress at the interface is given byn • T s •n +n • T •n =n • T l •n.…”

Section: Hydrodynamic Boundary Conditionsmentioning

confidence: 99%

“…There are few references addressing the experimental setup where the deformation of the scaffold has been considered to check the stiffness, elasticity, and strength of the scaffold used for bone tissue engineering and soft tissue engineering. [15][16][17][18] Based on the above literature, in the present work, we develop a mathematical model using biphasic mixture theory to study the cell growth inside a bioreactor with a deformable scaffold.…”

Section: Introductionmentioning

confidence: 99%

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Mathematical modeling of elastodynamics and cell growth inside a deformable scaffold fitted to the periphery of a bioreactor

Kumar

Sekhar

2021

Math Methods in App Sciences

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A mathematical model is developed for fluid flow, nutrient transport, and cell growth inside a bioreactor with a scaffold at the periphery and lumen at the centerline. The scaffold material is assumed to be deformable. In order to deal with the deformation of the solid phase and fluid phase inside the scaffold, biphasic mixture theory equations are adopted, which are derived from the theory of mixtures. The flow inside the lumen is governed by Stokes equation.Advection-diffusion-reaction equation is used for the mass balance of the nutrient within the scaffold region. Cell growth depends on the nutrient concentration and is expressed by the Contois equation that accounts for contact inhibition. We use lubrication approximation to reduce the system of hydrodynamic and nutrient transport equations. This leads to a coupled system of partial differential equations (PDEs) with time-dependent variables. Laplace transformation is used to deal with time-dependent terms, and Durbin's algorithm is used to retrieve the time dependency. We investigate the outreach of nutrients inside the scaffold region, which regulates the growth of cells at a particular time.Based on the available experimental data, we consider relevant reaction kinematics of the cells and observe the corresponding nutrient distribution inside the bioreactor. The factors that affect the nutrient concentration are lumen radius, porosity, and permeability of the scaffold, Thiele modulus, pressure gradient, and so forth. The total mass transfer rate is computed to understand the nutrient distribution across various regions of the bioreactor.

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Analysis of elastohydrodynamics and nutrient transport through deformable porous scaffold inside a hollow fiber membrane bioreactor

Kumar

Sekhar

2020

Physics of Fluids

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Hydrodynamics and nutrient transport in a hollow fiber membrane bioreactor is studied by developing a two-dimensional mathematical model in Cartesian coordinates. In a more realistic scenario, the scaffold is considered to be elastic and deformable, which undergoes deformation with the applied pore pressure. A mixture model is used to deal with the scaffold matrix, cells, and the fluid present in the scaffold region. The method of lubrication theory is incorporated when the aspect ratio of the lumen is small. The nutrient transport in the scaffold region is assumed to be governed by advection–diffusion–reaction mass balance due to the presence of cells and by advection–diffusion in the lumen and porous membrane. Analytical solution of the coupled system is presented for a short time scale where the cell growth, death, or differentiation is neglected. The results obtained focus on the effect of various parameters on the fluid flow, solid deformation, and consumption of nutrients due to different kinds of cells. It is observed that the deformation of the scaffold matrix increases monotonically with the flow rate supplied to the bioreactor. This behavior ensures that one can adjust the fluid flux to achieve optimum deformation in favor of cell growth and avoid damage of the scaffold. Moreover, a general criterion for the distribution of adequate nutrient concentration inside the bioreactor is developed to prevent the formation of the necrosis region inside the scaffold. Accordingly, the current investigation helps to arrive at suitable parameter combinations to monitor and control an ongoing experiment for optimum cell growth.

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Design and fabrication of micro/bio chip for in vitro fabrication of toroidal cellular aggregates

Cited by 3 publications

References 31 publications

Numerical Simulation of the Behavior of Toroidal and Spheroidal Multicellular Aggregates in Microfluidic Devices with Microwell and U-Shaped Barrier

Numerical Simulation of the Behavior of Toroidal and Spheroidal Multicellular Aggregates in Microfluidic Devices with Microwell and U-Shaped Barrier

Mathematical modeling of elastodynamics and cell growth inside a deformable scaffold fitted to the periphery of a bioreactor

Analysis of elastohydrodynamics and nutrient transport through deformable porous scaffold inside a hollow fiber membrane bioreactor

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