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Presented by
1)Phalke Rushikesh Pradip (862)
2)Shingate Nikhil Nandkumar (861)
3)Nikam Subodh Nivas (856)
4)Jankar Dipak Chandrakant (863)
5)Shinde Sourab Appaso (866)
6)Patil Parthesh Nandkumar (1161)
Under Guidance of
DR. A.B. Shinde
Abstract
1) Microfluidics has developed as a set of powerful tools that have greatly advanced in
some areas of biological research.
2) The use of microfluidics has enabled many experiments that are otherwise impossible
with conventional methods and is highly capable of providing advantages in terms of a
significant reduction in the sample processing time, sample volumes, and consumption
of costly reagents.
3) Various research groups have established continuous flow separation methods in
microfluidic devices; however, they have worked with relatively small dimension
microchannels (similar to the blood cell diameter).
4)The present work demonstrates separation of plasma by utilizing the Density effect in
microchannels with size of the order of mm.
5)The separation process exploits the phenomenon, which is very similar to that of
plasma skimming explained under Zweifach-Fung bifurcation law. The T microchannel
device design IS made in COMSOL MULTIPHYSICS SOFTWARE.
6)Three variables (fluid density, main channel width, and flow rate ) are identified as
the important parameters which define the device’s efficiency for the blood plasma
separation.
Chapter 1- Introduction
Chapter 2- objectives
Chapter 3- literature study
Chapter 4- Microchannel modeling
Chapter 5- Results and Discussion
Chapter 6- conclusion
Chapter 7- References
Chapter 1- INTRODUCTION
The separation of plasma from blood is an indispensable process in the domain
of disease diagnostics.
Human blood plasma provides crucial information pertaining to disease
diagnostics as innumerable biomarkers are found in blood plasma, which state
the physiological state of the human body.
Therefore, the plasma separation from whole blood is necessary for disease
diagnostics. The conventional method of plasma separation (centrifugation),
though commonly employed, is rather laborious and time consuming, and
cannot be integrated with a biosensor to develop a point of- care micro device.
The field of microfluidics has shown tremendous potential to provide distinct
insights and improvised solutions to processes involving complex traditional
experimental methods, especially in the areas of biology and clinical
diagnostics.
The excitement surrounding microfluidics rests on the fact that it is highly
capable of providing advantages in terms of a significant reduction in the
sample processing time, sample volumes, and consumption of costly reagents,
as well as precision in controlling fluid assays, among others.
1.1 Cetrifugation-
Plasma separation is achieved by subjecting the suspension to natural or induced gravitational fields. Blood
cells are denser than the liquid medium of plasma. These cells would settle down due to gravitational forces
and form a zone with a very high blood cell density. This method worth nothing that the method is used for
separating different blood cells. This is the conventional method and the commonly used method for
separating plasma, requires considerable amount of time and effort, and which cannot be integrated with a
biosensor to develop a point of- care device.
1.2 Blood-
Blood is a multiphase fluid, composed of cells suspended in plasma. The main components of blood are
erythrocytes (red blood cells), leukocytes (white blood cells), thrombocytes (platelets) and plasma. Blood
mainly comprises about 45%–50% red blood cells, ~1% of white blood cells and platelets, and the remaining
~55% is a pale or straw yellow colored fluid called plasma. Human blood plasma contains 91% water, 7%
proteins, 2% inorganic ions, and other organic substances. Blood exhibits a complex behavior even at a very
high concentration of cells and behaves as a fluid. Whole blood is a non-Newtonian fluid, whereas plasma is a
Newtonian fluid.
1.3 Definations-
RBC aggregation: The human blood tends to form reversible aggregates, sometimes referred to as ‘rouleaux’
formation. RBC aggregation is promoted by fibrinogen or plasma proteins.
Plasma skimming: The depletion of blood cells near the channel walls. It is utilized to withdraw plasma into a
side branch.
Bifurcation law: It states that: when RBCs flow through a bifurcation region of a capillary blood vessel, they
have a propensity to move into the daughter vessel, which has the higher flow rate, leaving a relatively small
number of cells in the lower flow rate vessel.
Chapter 2 OBJECTIVES
1.Literature study-
Our goal is to collect all information related plasma separation from blood. We collected 28 research paper related to
our project topic. By studing them we write the summary of each paper. After referring different literature we get the
idea for designing and manufacturing of microchannel. So we designed the Rectangular T- shape microchannel.
we design the different model of microchannel with different configuration, to study the effect of different geometries
inside the microchannel. It is found that each geometry like circle, semicircle, rectangle and square affect the blood
particle flow inside the microchannel . These affected blood flow results in different quantity and quality of plasma
separated from blood .we design T-shape microchannel in our design .The model diamension are less than 1cm.
We used the COMSOL MULTIPHYSICS SOFTWARE to analyse the result. The microchannel we created gives
satisfactory results in terms separation of plasma separation.
4)To validate the Simulation result with published data-
The result data we get after simulation demonstration in COMSOL MULTIPHYSICS software are match with
previously published research paper.
Chapter 3 Literature study
3.1 Microfluidic methods:
Microfluidic methods for blood plasma separation include both passive separation and active separation
methods. In non-inertial or active methods, separation is achieved by the application of external force fields such
as electrical and magnetic fields. However, to achieve separation, passive methods rely on effective microchannel
design, inertial effects, flow rate control, and utilize multiple biophysical effects such as the Fahraeus effect and
the Zweifach-Fung bifurcation law.
3.1.1 The active separation methods:
In non-inertial or active methods, separation is achieved by the application of external force fields such as
electrical and magnetic fields. Active systems generally use external fields (e.g., acoustic, electric, magnetic, and
optical) to impose forces to displace cells for sorting, whereas passive systems use inertial forces, filters, and
adhesion mechanisms to purify cell populations. Cell sorting on microchips provides numerous advantages over
conventional methods by reducing the size of necessary equipment, eliminating potentially biohazardous
aerosols, and simplifying the complex protocols commonly associated with cell sorting.
3.1.2 The passive separation methods:
Passive separation methods are mostly preferred because these methods do not require application of an
external force field, thereby allow for efficient system integration. Success in the passive method pertains to
intelligently manipulating themicrochannel pathways such that during blood flow, RBCs skim-off from whole
sample blood. The advantages of passive separation methods are their simplicity of design, ease of fabrication,
continuous operation, use of moderate to high flow rates, and ease of integration with a biosensor. Microdevices
based on passive separation methods for blood plasma separation are further classified as lateral displacement
by obstacles, sedimentation, filtration, and hydrodynamic effects.
3.1. Biophysical effects cell-free layer CFL:
1. In microcirculation, RBCs have a tendency to migrate towards the axis of the tube, thereby
increasing the cell concentration along the center while leaving a marginal zone devoid of cells
along the channel walls, called the cell-free layer (CFL).
2. Deformability of the cells is attributed as one of the reasons for the axial migration of cells; high
shear zones near the wall are also responsible for the axial migration of the cells. This in turn
increases the velocity of the RBCs compared to that of plasma. The cell-free layer thickness is
dependent on the cell concentration, deformability, vessel diameter, cell aggregation, and flow
rate. The thickness of the CFL decreases with an increase in tube diameter
3. Given different flow rates of the two daughter channels in the capillary bifurcation, the cell, on
reaching the bifurcation, faces a dilemma about choosing the channel flow to follow. Cells tend
to prefer the channel with the higher flow rate in comparison to the channel with the lower flow
rate
Chapter 4- Microchannel modeling
1 Xiangdong Xue, Mayur K. Patel, Maïwenn “Analysis of fluid separation in microfluidic T-channels”
Kersaudy Kerhoas, Marc P.Y. Desmulliez, Applied Mathematical Modelling 36 (2012) 743–755
Chris Bailey, David Topham
2 Wan Shi Low, Nahrizul Adib Kadri., “Computational Analysis of Enhanced Circulating
Tumour Cell (CTC) Separation in a Microfluidic
System with an Integrated
Dielectrophoretic-Magnetophorectic
(DEP-MAP) Technique” Chemosensors 2016, 4, 14
3 Ravishankar Dudhe, Sumathi Ayyalusamy, Ayesha “Microfluidics based Blood protein separation
Rashid and behavior modelling implemented using
COMSOL Multiphysics”
International Journal of Pure and Applied Mathematics Volume 118
No. 20 2018, 517-522
Jingjing Zhang, Xueyong Wei, Xiangdong Xue, and “Structural Design of Microfluidic Channels for
4 Zhuangde Jiang. Blood Plasma Separation”
Journal of
Nanoscience and Nanotechnology
Vol. 14, 1–8, 2014
James V. Green, Tatiana Kniazeva, Mehdi Abedi,
Darshan S. Sokhey, Mohammad E. Taslimb, “Effect of channel geometry on cell adhesion in microfluidic
devices” Lab Chip, 2009, 9, 677–685
5 Shashi K. Murthy .
Myung Gwon Leea, Joong Ho Shina, Sungyoung Enhanced blood plasma separation by modulation of inertial
Choib, Je-Kyun Parka. lift force” Sensors and Actuators B 190 (2014) 311– 317
6 Pavol Durca, Frantisek Foret, Petr Kuban.
7 “Fast blood plasma separation device for point-of-care
applications” Talanta 183 (2018) 55–60
Maiwenn Kersaudy-Kerhoas, Resham Dhariwal,
Marc P. Y. Desmulliez, Lionel Jouvet.
8 “Hydrodynamic blood plasma separation in microfluidic
channels” Microfluid Nanofluid (2010) 8:105–114
9 P. Sajeesh, Ashis Kumar Sen Siddhartha Tripathi, “Particle separation and sorting in microfluidic devices: a review” Microfluid
Y V Bala Varun Kumar, Amit Prabhakar, Nanofluid (2014) 17:1–52
14