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.