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Design, Simulation, and Fabrication of a Hybrid Inertial and Magnetophoretic Microfluidic Device for Target Cell Separation from Blood

Nasiri, Rohollah | 2021

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  1. Type of Document: Ph.D. Dissertation
  2. Language: Farsi
  3. Document No: 54646 (08)
  4. University: Sharif University of Technology
  5. Department: Mechanical Engineering
  6. Advisor(s): Shamloo, Amir; Akbari, Javad
  7. Abstract:
  8. Circulating tumor cells (CTCs) isolation from a blood sample has an important value in cancer research and its treatment. Microfluidics provides a great potential for target cell separation from biological samples by using different physical principles. Among the microfluidic cell separation methods, the inertial microfluidic devices are advantageous in handling samples for point-of-care diagnostics due to their simple structure, fast, label-free and low-cost characteristics. In this thesis, first, we designed and investigated the application of a symmetric serpentine inertial microfluidic device for the separation of CTCs from whole blood. For this purpose, numerical modeling was performed to analyze the fluid flow, particle movement and their trajectories within the channel to predict optimal operating condition for the proposed device. Then the device was fabricated using soft photolithography and suspension of two microparticles with size of 10 and 15 µm were injected into the microchannel separately to investigate the particles’ trajectories and focusing behavior at different flow rates. By using the proposed inertial separation approach, with a volumetric flow rate of 1000 µl/min and Reynolds number of 71, two types of particles with sizes of 10 and 15 µm particles, were successfully focused in distinct positions at the outlet of the channel that is desirable of separation of particles/cells. For cell experiment, MCF-7 cells as kind of CTCs are mixed with diluted human blood, and the mixed cell suspension was injected into this inertial device, and a maximum CTCs separation efficiency (~89%) ad purity of 84% for CTCs were attained at a flow rate of 1000 µl /min. Later, we investigated the combination of the inertial method with magnetophoretic cell separation method to separate CTCs from the blood sample in a single chip. First, the designed device was fabricated using the soft-lithography technique. Then, the CTCs were conjugated with magnetic nanoparticles and Ep-CAM antibodies to improve the magnetic susceptibility of the cells in the presence of the magnetic field by using permanent neodymium magnets of 0.51 T. Diluted blood samples containing nanoparticle-conjugated CTCs were injected into the device at different flow rates to analyze its performance. It was found that the flow rate of 1000 µl/min resulted in the highest separation efficiency and purity of ~95% and ~93% for CTCs, respectively
  9. Keywords:
  10. Secondary Flow ; Magnetic Fields ; Microfluidic System ; Circulating Tumor Cells (CTC) ; Cell Separation ; Cancer Cell Sepration ; Magnetic Nanodot ; Inertial Microfluidic Device

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