My Research
This section is devoted to my main research experience throughout my master's program.
Overview
I became interested in microfluidics technology and its important role in biomedical applications during my education in Sharif University of Technology. After gaining insight into various types of microfluidic platforms, I started my research on the mechanics of flow and particle/cell separation in microchannels, specifically the spiral microchannel. Since I wanted my work to be used in medical applications, I decided to work on the isolation of human white blood cells (WBCs) from whole blood. While comprising only about 1% of whole blood, white blood cells (WBCs) have a significant role in the body’s immune system and a change in their total number in the blood is the harbinger of infections, autoimmune reactions, and other malignancies. Thus, preparation of cell samples with suitable purities is required.
In my work, I developed a spiral microfluidic chip with decent working sample flow rate and white blood cell isolation efficiency and purity. The novel U-shaped cross section of the spiral microchannel allows the migration of red blood cells (RBCs) and platelets to the outer section of the microchannel while keeping the target white blood cells (WBCs) in the inner section. Additionally, it prevents the return of RBCs and platelets to the inner section of the spiral microchannel, hence removing the main drawback of spiral microchannels with rectangular cross-section. I employed a novel simulation technique by means of programming and developing a MATLAB-COMSOL Mutiphysics live-link in order to find the equilibrium positions of particles with various sizes within the spiral microchannel with any arbitrary cross-section geometry, hence allowing me to choose the best U-shaped geometry dimensions for my work.
I have done the relative researches, designing, fabricating and testing from 0 to 100 all by myself and experienced a great number of activities throughout my research, which helped me broaden my horizons in microfluidics and particle/cell separation techniques. Also, my research output have been published in Biosensors, a highly indexed journal paper, and an international conference paper (Link to Publications).
In my work, I developed a spiral microfluidic chip with decent working sample flow rate and white blood cell isolation efficiency and purity. The novel U-shaped cross section of the spiral microchannel allows the migration of red blood cells (RBCs) and platelets to the outer section of the microchannel while keeping the target white blood cells (WBCs) in the inner section. Additionally, it prevents the return of RBCs and platelets to the inner section of the spiral microchannel, hence removing the main drawback of spiral microchannels with rectangular cross-section. I employed a novel simulation technique by means of programming and developing a MATLAB-COMSOL Mutiphysics live-link in order to find the equilibrium positions of particles with various sizes within the spiral microchannel with any arbitrary cross-section geometry, hence allowing me to choose the best U-shaped geometry dimensions for my work.
I have done the relative researches, designing, fabricating and testing from 0 to 100 all by myself and experienced a great number of activities throughout my research, which helped me broaden my horizons in microfluidics and particle/cell separation techniques. Also, my research output have been published in Biosensors, a highly indexed journal paper, and an international conference paper (Link to Publications).
SimulationsIn order to have a better understanding of the mechanism of particle separation, I have done several case studies which examined the fluid domain, fluid flow over particles with different sizes, presence of the secondary flow and its role in inertial migration. It provided me with valuable insights into the nature of particle separation in curved geometries.
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ProgrammingEvery microfluidic device goes through a series of checkpoints before fabrication, including deep examinations and understanding of various parameters affecting its performance. Since this approach is bounded with trial and error, choosing an efficient method is crucial. In my research, I employed a novel strategy by setting a live-link between MATLAB as a coding program and COMSOL Multiphysics as a flow solver in order to calculate the equilibrium locations of particles in selected cross-sections of the spiral microchannel. It helped me predict and choose an optimum spiral geometry for my work and the flexibility of the code allowed me to try the calculations with different input geometries. Finally, an optimum microchannel design was selected and parallelization was done in order to boost the overall microchip throughput.
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MicromillingAfter being introduced to micromilling, I was given the chance to work with the "Dahlih MCV-1020A" machine. I became familiar with Autodesk PowerMill software as well in order to set and change the different parameters of the device, such as spindle speed, cutting rate and so on. I managed to fabricate my microfluidic plexiglass (PMMA) mold at this stage successfully.
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Soft LithographyI fabricated my chip using the standard soft lithography method. At this stage, after mixing and degassing the PDMS, it was cast onto the master mold and baked in a vacuum oven. After peeling off the cured PDMS layer and punching the holes, the final microchip was irreversibly bonded to a thick standard glass slab with an oxygen plasma and further baked to improve the bounding.
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Laboratory
During my laboratory work, I learned to use various devices and tools, such as syringe pump, sampler, fume hood, light microscope, inverted microscope, Neubauer chamber slide, steam sterilizer, polystyrene particles, and so on. I was given the chance to evaluate and validate my researches practically rather than focusing solely on theoretical aspects, such as simulations and calculations.
PreparationThe microchip was tested in various input flowrates in order to evaluate the PDMS-glass bounding and detect possible leakages. It was successful at the first attempt, tolerating a remarkable 8 ml/min flowrate throughout the chip without any damages. Since the two spirals worked in parallel to each other, it was necessary to provide an equal distributer to ensure that the same amount of flow rate is injected to both spirals. I made the distributor by modifying a three-way stop cock and put it into the test to ensure the equality of flowrates.
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Cell countThe first evaluation included the investigation of the device performance on the isolation of polystyrene particles with various sizes. It was done by preparing different mixtures having various particle concentrations and injecting them in the microchip using a syringe pump. After collecting the samples from the outlets, conventional cell counting technique was done using the Neubauer chamber in order to find the relation between the sample flowrate and isolation parameters.
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Blood testsLast but not the least, the performance of the microchip was put into the test by letting it process the input blood samples with different hematocrits in various blood sample flowrates.
It provided an optimum WBC isolation efficiency of over 95% and removing ratios of over 94% for RBCs and platelets for a 1% hematocrit blood sample. The optimum overall throughput of the microchip was 6 ml/min for the blood sample which is higher than the most reported microfluidic platforms. * Fun fact: I used my own blood as the input blood sample to my device. So let's say I poured my blood, sweat and tears into it. :D |
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Recap
Microfluidics is an interesting field of study which enables us, mechanical engineers, to share our knowledge and ideas with medical communities in order to help improve methods of experiments with an engineering theme to boost the overall progress. Nowadays, the importance of experiments and practical works has increased significantly. Theories are needed to put into various tests to ensure their validity. I was able to get a taste of practical work throughout my M.Sc. program, and despite facing quite a lot of challenges and hurdles, I enjoyed my laboratory experience and I would say it was definitely worth the try. I was marked "Excellent" upon defending my thesis later on as well which I'm proud of. I'm looking forward to experiencing more challenges in the future, specially lab work.