Loading...

In Silico Lung-on-a-Chip Simulation for Disease Modeling and Drug Delivery Purposes

Sarrami, Shadi | 2022

167 Viewed
  1. Type of Document: M.Sc. Thesis
  2. Language: Farsi
  3. Document No: 55067 (06)
  4. University: Sharif University of Technology
  5. Department: Chemical and Petroleum Engineering
  6. Advisor(s): Bastani, Dariush; Mashayekhan, Shohreh; Moghadas, Hajar
  7. Abstract:
  8. Organ-on-chip microfluidic devices create a three-dimensional and dynamic model that allows researchers to model diseases and test different drug candidates. In this regard, using a lung-on-a-chip microfluidic device, Covid-19 disease was numerically modeled. Initially, the distribution of oxygen concentration in the blood and respiratory membrane in the healthy state; when the respiratory membrane is the only barrier between air and blood; was found and observed that in this case, the length that the blood had to travel to reach full saturation was the same in the alveolar capillaries and the lung-on-a-chip microdevice. Then, to simulate the different phases of the disease, the formation of mucus and hyaline membrane on the respiratory membrane were considered as the characteristics of the silent hypoxia phase and the exudative phase of the disease and solubility, diffusion coefficient and effective diffusion coefficient for each were obtained by the similarity of these layers with hydrogels and plasma clots, respectively. The fibrotic changes of the respiratory membrane were considered the characteristic of the fibrotic and final phase of the disease. Fibrotic tissue's solubility and effective diffusion coefficient were obtained by similarity with the extracellular matrix with increased collagen content. At each stage, the amount of oxygen transferred to the blood was obtained by changing the thickness of the gas-blood barrier. It was observed that with increasing the thickness of the gas-blood barrier at each stage, the amount of oxygen transferred to the blood decreases. As the main purpose of the study, the amount of oxygen required in each stage of the disease for proper treatment of patients was obtained and it was observed that in the silent hypoxia stage of the disease, patients do not need oxygen therapy, which is in line with the mild nature of this stage. In the exudative and fibrotic stages of the disease, the amount of oxygen required by patients varies from about 18% to 75% for the exudative phase and from about 22% to 100% for the fibrotic phase, respectively.
    In the next step, the 20-nanometer particles’ deposition due to the similarity of their size with the exosome particles, as a drug candidate for the treatment of Covid-19; in the lung-on-a-chip microfluidic device with the associated velocity of air in the airways was simulated. The forces affecting the motion of nanoparticles of this magnitude are drag, Brownian and gravitational forces. The simulation results showed that the inlet air velocity of 0.612 mm/s due to the predominance of the Brownian force of the particles failed to deliver them to the cell culture section and all the particles were deposited in the inlet cylinder. Then, to deliver the nanoparticles to the cell culture section, strategies such as modifying the geometry of the device; to reduce the deposition of the particles in the inlet cylinder due to Brownian movements; And increasing the inlet air velocity to overcome the drag-to-Brownian force; was mentioned and observed that in the modified geometry to deliver nanoparticles to the cell culture section, the inlet air velocity can be increased to values of 25 mm/s and the shear stress obtained at the cell culture section will not damage the cells
  9. Keywords:
  10. Microfluidic Devices ; COVID-19 ; Numerical Simulation ; Nanoparticles ; Lung on Microchip ; Hyperbaric Oxygen Therapy ; Drug Testing ; Drug Delivery ; Organ on Chip

 Digital Object List

 Bookmark

No TOC