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Design, Simulation and Fabrication of Human Pulmonary Alveolus Model on a Microchip

Moghadas, Hajar | 2018

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 50518 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Saeedi, Mohammad Saeed
  7. Abstract:
  8. Microfluidic systems create great development in diseases and drug delivery in various organs of the body. In this study, human pulmonary alveolar cell performance was evaluated from the perspective of the cell culture using a microfluidic system. For this purpose, numerical simulations of the microchip channels flow field are very important to select appropriate models. So in the first step, the flow field and particle deposition were simulated. Then an optimal model was selected based on key parameters such as cell feeding, shear stress exerted on the cell, particles distribution and also the limitations and possibilities for constructing. The numerical results show that the shear stress, causing no inflammation and cell death. It was found that the shear stress induced by the medium culture flow is not so high to damage the cells and it is roughly uniform in the cell culture section (CCS). However, the local shear stresses in the other parts of the microchip differ by changing the angles of connection inlet. The results showed that the particle deposition was a function of the particle size, the properties of the fluid and the flow rate. At lower air flow rate, both small and large particles deposited in the entrance region and none of them reached the CCS. Once the air flow rate increased, the drag of the flow could overcome the diffusion of the small particles and deliver them to the CCS so that more than 88% of the 100 nm and 98% of the 200 nm particles deposited in the CCS. However, larger particles with average diameters in micrometers could not reach the CCS by the airflow even at high flow rate. In contract our findings indicated that both small and large particle could be delivered to the CCS by liquid flow. Our experimental data confirm that micro-particles (with diameters of 5 and 20 microns) suspended in a liquid can reach the CCS at well-adjusted flow rate. Consequently, a liquid carrier is suggested to transport large particles through microchannels. In the construction phase, cells maintenance scaffold were produced by electrospinning using the composition of the polymer PDMS and PMMA. This flexible and porous scaffold was prepared with proper tensile strength about 40% strain. The results of the MTT assay not only confirm the appropriate functioning of the scaffold in the cell culture. But also show that survival situation on the produced scaffold is better than pretreated commercial surface. In the next step, it was embedded as a separator membrane in the microchip. Colored fluid through channel confirmed no leakage. Cells were cultured in the microchip successfully. Scanning electron microscope images demonstrate the individual cells formation, the construction of monolayers of cells and the tumor mass into a microchip which provide unique condition for drug evaluation. Furthermore, it was shown that gold nanoparticles are not toxic to A549 cells
  9. Keywords:
  10. Numerical Simulation ; Gold Nanoparticle ; Micro/Nano Particle ; Drug Delivery ; Microfluidic System ; Lung on Microchip ; Pulmonary Alveolus Cell ; Electrospun Scaffold

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