Numerical study of microfluidic effects and red blood cell dynamics in 'deterministic lateral displacement' geometries
View/ Open
Vernekar2019.pdf (49.25Mb)
Date
03/07/2019Author
Vernekar, Rohan Ranganath
Metadata
Abstract
The last two decades have seen microfluidics gaining increasing interest from
the fields of medical diagnostics and bio-chemical processes, due to its immense
potential for point-of-care diagnostic applications. Since blood plays a
crucial role in many physiological and diagnostic processes, red blood cells
(RBCs) have been the focus of a large volume of microfluidics research. The
isolation of red blood cells and other blood components, based on the manifest
morphological characteristics, is required in many applications, e. g. flow
cytometry. The deterministic lateral displacement (DLD) is one such popular
microfluidic technique that has shown great promise toward cellular separations.
The DLD technique separates particles based on their hydrodynamic size.
It has been demonstrated for size-based separations down to unprecedented
size resolutions of ~ 10 nm. The DLD consists of a large number of obstacle pillars
placed in a microfluidic channel. The layout of these obstacles is such that
the obstacle array presents a fixed angle to the average fluid flow through the
microfluidic channel. Size-based separation comes about due to steric interaction
of particles with the pillars. Particles larger than a ‘critical’ size are forced
to move along the obstacle array incline. The larger particles, following the array
incline, are displaced perpendicular to the average flow direction, and are
said to be on the displacement mode. Particles smaller than this critical size
flow along the average fluid flow direction, zigzagging around the obstacles.
The trajectories followed by these smaller particles are classified as zigzag
mode. Micro-particles therefore follow different trajectory modes based on
their size, eventually leading to their spatial separation. The particles are separated
passively, i. e. other than the pressure drop needed to drive the fluid
flow through the DLD micro-channel, there is no need for any external forces
for particle sorting.
Numerous studies since the advent of the DLD have focussed on widening
the scope of applications covered by the technique. In this thesis, I take a more
physical approach, focussing on understanding the microhydrodynamics and
RBC dynamics within the DLD geometries. For these investigations, I have
used an in-house numerical solver that incorporates ingredients for fluid flow
solution, RBC membrane deformation, and an explicit coupling algorithm
between the two. The lattice Boltzmann method is used for obtaining a fluid
flow solution at low Reynolds numbers, and the finite element method is used
for computing the membrane energetics. The immersed boundary method
explicitly couples these two solutions with non-matching boundaries, at each
time step.
Firstly, I investigate subtle flow hydrodynamic effects through DLD obstacle
arrays. Here, fluid-only simulations uncover and map anisotropic flow permeability
of the obstacle arrays. The research reveals that if the unit cell of
the obstacle array geometrically forms a parallelogram, the array induces an
anisotropic pressure gradient normal to the average flow direction. Contrarily,
if the obstacle arrangement reflects a rotated square in its unit cell, anisotropy
is entirely absent. Such anisotropic pressure conditions in the DLD cause local
flow deviations and can lead to unintended particle motion arising from locally
varying critical separation size. I find that elevated levels of such anisotropy
are also brought about by pillar shape design and asymmetric array
gaps. Furthermore, strategies to minimise anisotropic flow effects are proposed.
The research on deformable RBC flow through the DLD tackles both single
and collective cell dynamics in these arrays. Single cell dynamics is studied
for special, non-cylindrical obstacle pillar shapes. In addition to the particle-obstacle
steric contact, dynamic RBC motion leads to effects that influence
cell trajectories in the DLD. Such effects are strongly tied to the interplay
between RBC deformability, dynamic motion (such as tumbling and tank-treading)
and the flow-field generated by the pillar shape. In certain cases,
wall-induced hydrodynamic cell migration becomes significant enough such
that the deformed tank-treading RBC undergoes displacement mode without
steric contact with the pillars. Here, migration velocity experienced by the
cells interacting with special pillar shapes causes a reversal of the phase-bifurcation
trend. The uncovering of this mechanism, opens the door for research
on novel DLD pillar designs that exploit wall-induced soft particle
migration.
Lastly, the research turns to collective RBC dynamics at high volume fractions,
in standard DLD arrays with cylindrical pillars. Here, I research the effect
of increasing cell volume fraction on the displacement and zigzag modes,
with the help of appropriate statistical measures. I find that the displacement
mode suffers a breakdown at higher volume fractions, while the zigzag mode
remains robust. This has important implications for cell separation applications
in the DLD, where smaller particles (e. g. platelets) need to be separated
from a dense background of RBCs and vice versa.
The investigations undertaken in this thesis identify subtle hydrodynamic
and particle effects in DLD arrays that explain previously unresolved particle
behaviour. This research should help improve the design and fabrication of
DLD devices, especially those targeted at improved separation and manipulation
of deformable RBCs.