The document describes a numerical analysis of a hybrid micro-separator that uses magnetophoresis and hydrodynamic forces to separate blood cells. The separation exploits differences in physical and magnetic properties between red blood cells (RBCs) and white blood cells (WBCs). Simulation results showed over 80% separation efficiency for RBCs and over 90% for WBCs, indicating the device can efficiently separate blood cell types without labeling based on RBCs' paramagnetic property. The micro-separator could be useful for lab-on-a-chip diagnostic devices.
1. Label-free Microfluidic Blood Cells
Micro-separator
Foughalia Aissa and S. Noorjannah Ibrahim
Department of Electrical and Computer Engineering,
International Islamic University Malaysia
P.O. Box 10, 50728 Kuala Lumpur, Malaysia
IEEE-DTIP 2016
3. oThe paper presents numerical analysis in 3D of an hybrid micro-
separator that uses magnetophoresis (MAP) and hydrodynamic forces for
blood cells separation.
oThe separation between red blood cells (RBC) and white blood cells
(WBC) is done by manipulating the differences of their physical and
magnetic properties .
oThe analysis was conducted using finite element software, COMSOL
Multiphysics®.
Introduction
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4. o Separation of blood cells is essential for;
diagnostic purposes
stem cell research
clinical applications
o A precise control over the cell during separation process is essential for
more fast, gentle, and coordinated manipulation of the living cells, and
therefore more precise and better quality analysis.
oThe density-gradient centrifugation is the most common technique
for blood cell separation based on intrinsic densities differentiation but it
does not have the capability of handling very small volume of
blood.
Introduction
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5. Many microfluidic methods of blood separation have emerged in the
past decade to scale down the analysis to extremely small
volumes.
Microfluidics-based cell separation
methods
Hydrodynamics
Magnetophoresis (MAP)
Structural filters
Dielectrophoresis (DEP)
Acoustophoresis
...etc
Introduction
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6. Introduction
The hybrid blood micro-separator can be used as a secondary module for
a lab on chip (LOC) diagnostic device as described in figure(1).
Fig.1: LOC device for the blood diagnosis.
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7. o Hydrodynamic is a passive separation technique that separates cells
of interest by controlling flow rate through, channel geometry, and
configuration of outlets.
o The hydrodynamic velocity flow vector Uhyd can be determined by
solving the Stokes equation for laminar flow in the microchannel. [1]
Introduction
[1] Bruus, Theoretical microfluidics. Oxford ; New York: Oxford University Press, 2008
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8. Magnetophoresis force (FMAP) occurs as a result of magnetic field
(external magnet) acting on magnetic susceptible particles such as the
blood cell creating an interaction of magnetic dipole moment of the blood
cell with the external applied magnetic field.[2]
Magnetophoretic force on a blood cell placed in the plasma solution
Magnetophoresis method separate particles based on their magnetic
characteristics.
Mainly, RBCs are paramagnetic while all the other cells including WBCs
are diamagnetic.
Introduction
[2] Zborowski et al. “Open Gradient Magnetic Red Blood Cell Sorter Evaluation on Model Cell Mixtures,” IEEE
Trans. Magn., vol. 49, no. 1, pp. 309–315, Jan. 2013
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9. Methodology
Design and simulation are developed using COMSOL Multiphysics®
Fig .2: Model description of the blood micro-separator showing its
geometrical parameters.
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10. Methodology
The simulation is performed with the assumption that;
• The plasma’s relative permeability is 1.05. [3]
• RBCs and WBCs are considered to be spherical, and the typical
value of their density (ρ) is 1125 kg/m3. [4]
• The diameters of RBCs and WBCs are 6µm and 13µm respectively
• RBCs and WBCs have no electrical charge.
• The magnetic susceptibility of deoxygenated RBCs is 3.9×10-6 SI
and of WBCs susceptibility is -9.2×10-6 SI. [3]
[3] M. Hejazian, W. Li, and N.-T. Nguyen, “Lab on a chip for continuous-flow magnetic cell separation,” Lab
Chip, vol. 15, no. 4, pp. 959–970, 2015
[4] J. Jung and K.-H. Han, “Lateral-driven continuous magnetophoretic micro-separator for separating blood
cells based on their native magnetic properties,” 2009, pp. 620–623.
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11. COMSOL Products Used:
AC/DC Module
Microfluidics Module
Along with the Particle Tracing Module
Methodology
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For Particles tracing the particles respond to both Drag and MAP
Forces.
Key Elements
Simulating a magnetic field induced by the permanent magnet
Simulating microfluidic flow in the micro-channel
Using Particle Tracing to analyze the cells respond to magnetophoretic
and hydrodynamic drag forces.
The separation force of each particle is the summation of both forces;
the MAP force and the hydrodynamic force.
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12. Methodology
In the analysis, COMSOL solves Maxwell's equations for magnetic
field and Stokes equations for fluid flow.
It is expected that the blood cells would be subject to the FMAP as the
counted is perpendicular to the magnetic flux density of the
ferromagnetic wire.
RBCs (paramagnetic particles) would experience a force pushing
them away from the ferromagnetic wire in the microchannel inner
wall and thus they would be directed to outlet-1 and outlet-2
respectively.
BB ).(
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13. Results
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The same number of WBCs and RBCs released at the inlet was
predefined in each case. A total number of 50, 100 and 200 particles of
each type was released from the inlet in orders to evaluate the
separation efficiency.
The number of particles extracted from each outlet was evaluated in
various cases using the global evaluation option provided by COMSOL
Multiphysics®.
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The results in the Table bellow present the RBCs and WBCs counts in
different outlets in various cases where 50, 100 and 200 particles were
released from the inlet.
The number of particles at outlets was determined at the moment when all
the particles are extracted, which is generally at 20s in the selected cases.
Number
of particles at
the inlet
Number of particles at outlets
Outlet-1 Outlet-2 Outlet-3
RBCs
50 42 3 5
100 81 9 10
200 165 16 19
WBCs
50 3 1 46
100 7 3 90
200 12 5 183
Table 1. Simulation results indicating numbers of WBCs/RBCs extracted at each
outlet of the micro-separator.
Results
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Results
The separation efficiency was calculated using the following Equation
.
Where NOutlet, and NInlet are the, the number extracted particles
(RBCs/WBCs) at the respective outlet, and the number of particles
(same type) released at the inlet, respectively
RBCs (relatively smaller than WBCs) are pushed toward outlet-1 by the
hydrodynamic force as they drifted by the high velocity fluid flow.
WBCs continue their movement along the micro-channel because of the
MAP force resulted by the highly magnetized ferromagnetic wire that helps
WBCs to be pulled toward the inner wall of the channel
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Results
Fig.3 Simulation results with percentage at each outlet indicating the
average separation efficiency of RBCs and WBCs.
The ratio of particles extracted from each outlet over the total number of
particles was determined in terms percentage as illustrated in Fig.3
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Results
The analysis of the results revealed that a high separation efficiency
(approximately 91%) of WBCs and could be obtained from a single sample
solution containing both WBCs and RBCs.
The average separation efficiency of RBCs is relatively high at outlet-1
(approximately 82%).
The results of separation efficiency are identical and consistent with the
results of the 3D model the previous section.
This indicates that the proposed U-shaped micro-separator is capable of
separating RBCs and WBCs efficiently.
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18. In this work, the micro-separator uses the combination of Magnetophoresis
with hydrodynamics in order to separate white blood cells (WBCs) and red
blood cells (RBCs) by taking into account the magnetization of the
ferromagnetic elements and fluidic forces on the cells.
The simulation of blood cells’ movements on the micro-separator, were
profiled and show a successful separation between RBCs and WBCs by using
the MAP and hydrodynamic forces.
The separation can be done without any labeling process due to red blood
cells paramagnetic property.
Overall, the platform presented in this work provides insights of challenges
associated with blood separation towards the realization of better diagnostic
devices and it might be used for other application as well.
Conclusion
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19. Acknowledgment
,The authors greatly acknowledge the FRGS financial support under grant
number 13-024-0265 from the ministry of education, Malaysia.
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