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Faisal Ahmed
BioE PhD Defense
Date: Tuesday, Aug 29, 2017
Time: 9-11 AM
Location: MRDC Conference Room 4211
Committee members:
Dr. Cyrus Aidun (Advisor)
Dr. Gilda Barabino(Advisor)
Dr. Edward Botchwey
Dr. Brandon Dixon
Dr. Wilbur Lam
Title: MICROFLUIDIC DEVICES FOR STIFFNESS DEPENDENT ENRICHMENT OF
RED BLOOD CELL SUBPOPULATION
Red blood cells being the most dominant cell type of blood are often the target of many
hematologic diseases such as sickle cell disease, malaria, spherocytosis and some types of
cancers. In addition to affecting biological properties, these diseases also alter biomechanical
properties such as morphology, size and stiffness of red blood cells. Separating or enriching
the cellular components of blood into subpopulation based on their bio-mechanical
properties and analyzing them have the potential to lead to enhanced strategies for assessment
and treatment of these diseases. Current techniques and equipment for diseased cell
sample enrichment are time consuming, expensive and need well trained professionals to
be conducted. Microfluidic platform based red blood cell enrichment device is one of the
most promising technologies that are currently the subject of considerable interest among
researchers because of its low cost, high throughput, easy operation and the potential to
do enrichment within the physiological flow condition. In this research work, microfluidic
devices were designed, fabricated and tested for enriching red blood cell subpopulations
based on their stiffness from a mixture of stiff and normal red blood cells. In the first portion
of the work, lab developed numerical simulation tools were deployed to study stiffness
dependent margination pattern of red blood cells in high aspect ratio straight microchannels
with rectangular cross-section. Stiff red blood cells were observed to marginate near the
channel walls whereas normal (and hence more deformable) red blood cells were observed
to marginate around the center line of the channel regardless whether cell-cell interaction
was significant or not. Cells of different stiffness reached to their equilibrium locations
faster in channels with smaller cross sections. Increasing flow Reynolds number and hence
the flow rate resulted in stronger segregation between normal and stiff red blood cells for
the whole range of Reynolds numbers for which simulations were run. Increasing cell volume
fraction in solution also boosted separation between cells of different stiffness. Based
on the findings of the simulations, two types of cell enrichment devices were designed and
fabricated, simple straight channel device and multistep device. The simple straight channel
device was tested for a wide range of flow Reynolds number and cell volume fractions.
Simple straight channels were observed to perform better with increasing flow Reynolds
number and cell volume fraction up to certain threshold for each of them, and after that
threshold there was no significant improvement of performance. Numerical simulations
were conducted with parameters matching with some of the experiments and the results
obtained were remarkably close to those from the experiments. Statistical analysis on experimental
data found the effect of individual parameters, flow Reynolds number and cell
volume fraction, to be significant. It also revealed that there was significant interaction between
the factors flow Reynolds number and volume fraction. This implies that the extent
of the effect of one factor (e.g. flow Reynolds number) changes when the value of the
other factor (e.g. volume fraction) varies. The multistep device was also tested for different
combinations of flow Reynolds number and cell volume fraction and, was observed
to perform 1.6 times to 3.15 times better in enriching stiff cells from a mixture of stiff and
normally deformable red blood cells. To our knowledge this is the first study that incorporated
such rigorous multiphysics simulations to support experimental study on stiffness
dependent margination of red blood cells in straight micro-channels. This research work
revealed previously unreported information about stiffness dependent cell enrichment with
simple straight channel microfluidic device and proposed a new device that performed significantly
better than the simple straight channel device.
