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Design of Microfluidic Chip for 3D Cell Culture

Ghobadi, Faezeh | 2022

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  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55149 (06)
  4. University: Sharif University of Technolog
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Saadatmand, Maryam
  7. Abstract:
  8. Understanding biological systems requires extensive knowledge of individual parameters, and to study the processes of cell differentiation and cell behavior, a suitable environment must be created with the physiological conditions of the human body. For this purpose, with the knowledge of microfluidics, a microenvironment can be provided to study the behavior of cells on a small scale. The use of bone tissue model microfluidic chips is an alternative and new method in which it is possible to study the behavior of cells to differentiate into bone and to examine the toxicity of drugs, which in itself can help in the effective and successful treatment of these cases show. Therefore, in this study, to build a microfluidic chip to mimic bone tissue, mass transfer simulation and fluid transfer were performed with Comsol software to obtain the appropriate geometric dimensions of the chip. The equations of flow and motion of collagen solution were solved using initial conditions, boundary conditions, suitable parameters, and a two-phase module. Mass transfer simulations were performed for different dimensions of trapezoids, and fluid simulations were performed by changing the dimensions of trapezoids, changing the distance between them, and the effect of collagen solution viscosity. The results showed that in the proposed geometry, the appropriate dimensions of the trapezoid are a small base of 100, a large base of 200, and a height of 200. The distance between the trapezoids is 100 m, and the most suitable concentration of collagen solution to prevent leakage is 3 mg/ml. With the right geometry and timing, the culture medium penetrates the hydrogel channel and the collagen solution moves along the channel without leakage.Also, after obtaining the optimal dimensions of the simulation, a microfluidic chip was fabricated using photolithography. In this study, we investigate the viability of these cells in the chip by creating a bone microenvironment on a 3-channel microfluidic chip and a three-dimensional culture of L929 fibroblast cells inside a 3 mg/ml collagen hydrogel matrix with bioactive glass nanoparticles. Microfluidics and obtaining the optimal concentration of bioactive glass were investigated. In this way, collagen was extracted from the rat tail and its characterization was evaluated by FTIR and SDS-PAGE tests. The bioactive glass was synthesized by the sol-gel method and its characterization was evaluated by XRD, FTIR, FESEM, DLS, and EDAX tests. The mechanical properties of collagen hydrogels with bioactive glass nanoparticles were investigated by rheological testing. By the MTT test, the optimal concentration of bioactive glass was selected to be 3% and live/dead staining was performed to evaluate cell viability.
  9. Keywords:
  10. Microfluidic Chip ; Collagen ; Simulation ; Bioactive Glass ; Three Dimentional Cell Culture ; Human Dermal Fibroblast Cell

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