status confirmation for master’s thesis...
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UNIVERSITI TUN HUSSEIN ONN MALAYSIA
STATUS CONFIRMATION FOR MASTER’S THESIS
DEVELOPMENT OF A MICROFLUIDIC DILUTION AND INFUSION
PUMP SYSTEM
ACADEMIC SESSION : 2015/2016
I, MUHAMMAD SHARIL BIN SARIPAN agree to allow this Master’s Thesis to be kept at the
Library under the following terms:
1. This Master’s Thesis is the property of Universiti Tun Hussein Onn Malaysia.
2. The library has the right to make copies for educational purposes only.
3. The library is allowed to make copies of this report for educational exchange between
higher educational institutions.
4. ** Please Mark (√)
CONFIDENTIAL
(Contains information of high security or of great
importance to Malaysia as STIPULATED under the
OFFICIAL SECRET ACT 1972)
RESTRICTED
(Contains restricted information as determined by
the Organization/institution where research was
conducted)
FREE ACCESS
_________________________
Approved by,
__________________________
(WRITER’S SIGNATURE)
(SUPERVISOR’S SIGNATURE)
Student’s name
MUHAMMAD SHARIL BIN
SARIPAN
Date: ___________________
Supervisor’s name
PM.DR. SOON CHIN FHONG
Date : ________________________
NOTE:
** If this Master’s Thesis is classified as CONFIDENTIAL or RESTRICTED,
Please attach the letter from the relevant authority/organization stating
reasons and duration for such classifications.
28 JANUARY, 2016 28 JANUARY, 2016
DEVELOPMENT OF A MICROFLUIDIC DILUTION AND INFUSION PUMP
SYSTEM
MUHAMMAD SHARIL BIN SARIPAN
A thesis submitted in
Fulfillment of the requirement for the award of the
Degree of Master of Electrical Engineering
Faculty of Electrical & Electronic Engineering
Universiti Tun Hussein Onn Malaysia
JANUARY, 2016
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I hereby declare that the work in this thesis is my own except for quotations and
summaries which have been duly acknowledged.
Student : ………………………………………………..
Muhammad Sharil bin Saripan
Date : ……………………………………………….
Supervisor : ………………………………………………..
PM Dr Soon Chin Fhong
Date : ……………………………………………….
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ACKNOWLEDGEMENT
First of all, all grateful to Allah SWT, our creator for his merciful and bless to all
people. I would like to give a million thanks to my parents for all the support and
motivation for me during my Postgraduate program over past one years and six
months here. Without them, I can’t achieve my dream as I was here. I am very
pleased with all their sacrifice as the backbone to ensure that I can be a good person
for them and to graduate my studies soon. Special thanks also to PM Dr. Soon Chin
Fhong, with her supervision and guidance for these one year on my final year project,
the whole progress of my master project goes smoothly. The appreciation goes to my
supervisor for the cooperation to ensure my project work progress kept on the track.
Also a million thanks to the Suria Arts and MyBotic Company.
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ABSTRACT
In recent years, there are many biological studies that require a use of microfluidic
device in the experiment, one of the device used is dilution chip which it used to
separate the concentration of the fluid intensity for many application. One of the
application use the dilution chip is for cytochemical treatment. Thus, to separate the
fluid intensity in the microfluidic chip, an infusion pump has been developed with an
aim to drive fluid into the microfluidic device with different flow rate set. The flow
rate set in the infusion pump is 0.5, 1 and 2 ml/min. The purpose of applying
different flow rates used to test the efficiency of the dilution in microfluidic chip
with different flow rates. The infusion pump system built by using Arduino as the
main microcontroller to control the whole system operation including for both of
infuse and diffuse process by using bipolar stepper motor and motorized linear slider
to control the plunger movement.
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ABSTRAK
Pada tahun terkini, banyak kajian penyelidikan dalam bidang biological yang
memerlukan penggunaan microfluidic cip dalam pengujian makmal, antara salah satu
contoh alatan yang digunakan adalah microfluidic cip pencairan yang digunakan
untuk proses mencairkan kelikatan cecair yang digunakan. Salah satu aplikasi
pencairan yang digunakan dalam pengujian adalah rawatan cytochemical. Oleh yang
demikian, untuk memisahkan kelikatan cecair didalam microfluidic cip, satu infusion
pam telah dibangunkan dan direka dengan tujuan untuk mengalirkan cecair ke dalam
microfluidic cip dengan kadar pengaliran yang berbeza. Kadar pengaliran yang telah
ditetapkan didalam system pam adalah 0.5, 1 dan 2 ml/min. Tujuan kadar pengaliran
yang berbeza untuk melihat keberkesanan pencairan di dalam microfluidic cip.
Infusion pam dibina dengan menggunakan Arduino sebagai pengawal utama
keseluruhan system operasi termasuk proses infuse dan diffuse dengan menggunakan
motor pelangkah jenis bipolar dan penggerak lurus bermotor untuk mengawal
pergerakan penarik picagari.
vi
TABLE OF CONTENTS
CHAPTER TITLE PAGE
DECLARATION i
ACKNOWLEDGEMENTS iii
ABSTRACT iv
ABSTRAK v
TABLE OF CONTENTS vi
LIST OF FIGURE ix
LIST OF TABLE xiii
CHAPTER 1 INTRODUCTION 1
1.1 Microfluidic background 1
1.2 Project background 1
1.3 Problem statement 2
1.4 Objectives of project 2
1.5 Project scopes 3
CHAPTER 2 LITERATURE REVIEW 4
2.1 Physics of microfluidic 4
2.1.1 Reynold’s number 4
2.1.2 Fluidic resistance 5
2.1.3 Beer’s lambert law 5
2.2 Fabrication of microfluidic 6
2.2.1 Photolitography 6
2.2.2 Master molding process 7
2.2.3 Advantages and disadvantages of PDMS 8
2.3 Types of infusion syringe pump 9
2.3.1 Neonatal syringe pump 9
2.3.2 In-line gear pump 10
vii
2.3.3 Self-aligning gas or liquid micropump 11
2.3.4 Micro-jet pump for microfluidic system 12
2.4 Micromixer dilution 13
2.4.1 Types of microfluidic mixer 14
(a) Single-target dilution microfluidic 14
(b) Digital microfluidic biochip 15
(c) Rectangular mixing channel 15
(d) Vibrating microplate mixer 16
(e) Serial dilution micromixer 16
(f) Straight, square wave and 3D
serpentine micromixer
17
(g) One channel micromixer 18
2.4.2 Applications of microfluidic mixers 18
2.5 Comparison of previous projects 19
CHAPTER 3 METHODOLOGY 24
3.1 The flow chart of the project 24
3.2 Development of the infusion pump system 26
3.2.1 Block diagram of the infusion syringe
pump system
26
3.2.2 Operation of the infusion pump system 28
3.3 Design and development of the infusion pump 29
3.3.1 Simulation of the electronic circuit
simulation
29
3.3.2 Prototype design of the infusion pump
device
31
3.4 Characterization of linear slider rotation speed 32
3.5 Design of the microfluidic mixer device 33
3.6 Design of microfluidic dilution chip using
COMSOL multiphysics version 5.1 software
34
3.7 Microfluidic fabrication process 36
3.8 Absorbance of the fluid dilution calculation 39
3.9 Arduino programming 39
viii
CHAPTER 4 RESULTS AND DISCUSSION 49
4.1 Introduction 49
4.2 Simulation of the mixing function at the merging
channel result
49
4.3 Main menu system interface functions 50
4.4 The infusion pump system model developed 51
4.5 Motorised linear slider produced 52
4.6 Flow rate calibrations test 53
4.7 Calibration result analysis 56
4.8 Calibration results of stepper motor speed 58
4.9 Dilution concentration result 60
4.10 Dilution spectrum 62
4.11 Determine the concentration of the green fluid dye
at wavelength of 330
63
(a) High concentrate dilution concentration 63
(b) Less concentrate dilution concentration 64
(c) Less diluted dilution concentration 64
(d) Much diluted dilution concentration 65
4.12 Drawbacks of the project development 66
CHAPTER 5 CONCLUSION 67
5.1 Future improvements and suggestions 67
REFERENCES 68
APPENDIX A (ZD-6560-V3 2.5A MOTOR DRIVER) 70
APPENDIX B (LCD DISPLAY) 71
APPENDIX C (FULL CODING) 72
ix
LIST OF FIGURE
Figure 2.1 (a) Tube channel of microfluidic 5
Figure 2.1 (b) Formula used to calculate fluid resistance 5
Figure 2.2 (a) Absorption sample of concentration 5
Figure 2.2 (b) Beer’s lambert law formula 5
Figure 2.3 Photolithography process 7
Figure 2.4 Master mold process 7
Figure 2.5 (a) Novel mechanical syringe pump design 9
Figure 2.5 (b) Measurement result 9
Figure 2.6 (a) Magnetic coupling structure of in-line gear pump 10
Figure 2.6 (b) Flow rate versus pump rotation speed for
theoretical and measurement in-line gear pump
10
Figure 2.7 (a) Measurement setup for micropump illustration 11
Figure 2.7 (b) Measurement result for the flow rate 11
Figure 2.7 (c) Measurement setup for gas pump 12
Figure 2.7 (d) Measurement result for gas pump 12
Figure 2.8 (a) Image of micro-jet pump fabricated 13
Figure 2.8 (b) Schematic diagram of micro-jet pump 13
Figure 2.9 Classification scheme of micromixer 14
Figure 2.10 Top and cross-sectional view of digital
microfluidic (DMF) biochip
14
Figure 2.11 Schematic design of digital microfluidic biochip 15
Figure 2.12 Block diagram of setup for mixing pressure-
driven microfluidic
15
Figure 2.13 Channel of microfluidic geometry and operating
parameter
16
Figure 2.14 Channel of microfluidic design using COMSOL 16
Figure 2.15 Graphical abstract for serial dilution experiments
of microorganisms’ growth in bacteriological
17
Figure 2.16 3 types of micro-channel used to determine the
fluid velocity in micro-channel
17
x
Figure 2.17 Schematic of two input reservoir of microfluidic
to mix two different fluid
18
Figure 3.1 Flow chart for project methodology 25
Figure 3.2 Block diagram of the mechanical system 26
Figure 3.3 Illustration block diagram of infusion pump 27
Figure 3.4 Flow chart operation of infusion pump system 28
Figure 3.5 The circuit controller, input switches and output
indicators
29
Figure 3.6 Direction and stepping pin connected to the
Arduino board from motor driver ZD-6560-V3
30
Figure 3.7 LCD display connection pin 31
Figure 3.8 Prototype infusion pump device 32
Figure 3.9 Digital laser tachometer 33
Figure 3.10 (a) Finished microfluidic dilution sticker template 34
Figure 3.10 (b) Paint illustration of microfluidic dilution device 34
Figure 3.11 Design of microfluidic dilution and mixing using
COMSOL software
35
Figure 3.12 Stick template to petri dish 36
Figure 3.13 Coating of microfluidic 36
Figure 3.14 Heating process was used to cure the PDMS and
vacuum process used to remove bubbles
37
Figure 3.15 Microfluidic pattern heated 37
Figure 3.16 Remove microfluidic pattern 38
Figure 3.17 Coated PDMS mixture and reheated 38
Figure 3.18 Create hole and tubing pipe installation 38
Figure 3.19 Complete microfluidic device 38
Figure 3.20 Absorbance formula for difference the dilution
result
39
Figure 3.21 Header files source code 39
Figure 3.22 Pin declaration for input and output port 40
Figure 3.23 Stepper pin configuration 40
Figure 3.24 Connection from ZD-6560-V3 motor driver to
Arduino pin
41
xi
Figure 3.25 Pin used to active the liquid crystal 41
Figure 3.26 Declaration for the push button 41
Figure 3.27 Startup program to initialize the LCD 42
Figure 3.28 Void function for slow speed 42
Figure 3.29 Void function for medium speed 43
Figure 3.30 Void function for high speed 43
Figure 3.31 Void reverse function 44
Figure 3.32 Void stop function 44
Figure 3.33 Loop process function 45
Figure 3.34 Selective program “A” 46
Figure 3.35 Selective program “B” 46
Figure 3.36 Selective program “C” 47
Figure 3.37 Selective program “D” 47
Figure 3.38 Selective program “E” 48
Figure 4.1 Simulation result for the velocity of the fluid flow
in the microfluidic channel
50
Figure 4.2 Main menu interface message 50
Figure 4.3 Flow rate of 0.5 ml/min button process 50
Figure 4.4 Flow rate of 1 ml/min button process 51
Figure 4.5 Flow rate of 2 ml/min button process 51
Figure 4.6 Linear slider move in reverse process 51
Figure 4.7 Model of the infusion pump designed 52
Figure 4.8 Structure design of the linear slider 53
Figure 4.9 Graph flow rate of 0.5 ml/min collected from the
repetition of 3 experiments
54
Figure 4.10 Graph flow rate of 1 ml/min collected from the
repetition of 3 experiments
55
Figure 4.11 Graph flow rate of 2 ml/min collected from the
repetition of 3 experiments
56
Figure 4.12 Graph shows the flow rate collected at different
step size
57
Figure 4.13 Graph analysis between the relationship of flow
rate with speed and step size measured
58
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Figure 4.14 RPM result comparison 59
Figure 4.15 Motor speed result with and without syringe
inserted
60
Figure 4.16 Dilute concentration of fluid in microfluidic chip 61
Figure 4.17 Different types of fluid concentration obtained
from the three outlets of microfluidic mixer device
for a flow rate of 2 ml/min
61
Figure 4.18 Light absorbed from different fluid concentration 63
Figure 4.19 Concentration obtained from the high concentrate
solution
64
Figure 4.20 Concentration obtained from the less concentrate
solution
64
Figure 4.21 Concentration obtained from the less diluted
solution
65
Figure 4.22 Concentration obtained from the much diluted
solution
65
Figure 4.23 Absorbance of different dilution with the
concentration collected
66
xiii
LIST OF TABLE
Table 2.1 Applications of Microfluidic mixer used in the previous
project developed
18
Table 2.2 Comparison of different syringe pump systems for use
with microfluidic device
20
Table 2.3 Comparison between project application techniques in
microfluidic device
21
Table 3.1 Parameter set on the microfluidic input channel 35
Table 3.2 Material parameter set for water in inlet channel 35
Table 3.3 Material parameter for the green food colouring dye 36
Table 4.1 Calibration result for 0.5 ml/min flow rate by using step
size of 280 with 3 different result
53
Table 4.2 Calibration result for 1 ml/min flow rate by using step
size of 560 with 3 different result
54
Table 4.3 Calibration result for 2 ml/min flow rate by using step
size of 1120 with 3 different result
55
Table 4.4 Collected data from calibrating test 57
Table 4.5 RPM measurement result comparison 59
Table 4.6 Motor speed test from flow rate result with load and
unloaded syringe
60
Table 4.7 Total absorbance of light for different dilution 62
Table 4.8 Concentration of green food colouring dye obtained
from different dilution result
65
1
CHAPTER 1
INTRODUCTION
1.1 Microfluidic Background
Microfluidic is a multidisciplinary field that investigates the behaviour of fluids itself
at the micro scale to pico scale of fluid [1] The application of microfluidic devices
are such as the chemical reaction, control volume of fluid or to manipulate small
samples volume such as for lab-on-chip application [1,2]. Channels in the
microfluidic device can be used to control the movement of fluids in micro or nano
metric volume. Polydimethylsiloxane (PDMS) is the main material used for the
manufacturing of micro-fluidic device [3,4]. In this project, a microfluidic device
will be used as an input for the fluid injected by the infusion pump.
1.2 Project background
In this part, the project of microfluidic fabricated for dilution of solvent purpose to
determine the force ex. The solvent injection system consists of a customized syringe
pump. The main important thing for this micro-fluidic device is the syringe pump
system that assembles together with it. The syringe pump act as an infusion to
control the flow rate of the fluid flow through a micro-fluidic devices channel.
2
The syringe pump will made up with 2 mode of microfluidic device, which will use
infusion process for both solvent and distilled water. The purpose for the project
develop to separate the concentration of chemical solution by infuse a volume of
distilled water then mix with an amount of chemical solution to find the
concentration of the solution by using dilution process. , the 2 tier of microfluidic
will design with 4 outlets for the dilution process. The 2 tier input will be the distilled
water and solvent, both of the substances will flow through the 4 flow channel of
microfluidic to mix both solution to separate the concentration obtain through the 4
outlet of the microfluidic device.
1.3 Problem Statement
Current problem occurred in the design of syringe pump system was the control of
speed and the volume flow in µl/min. The problem were not satisfies some user
when they handling some experiment for the micro-fluidic. In other word, the drive
of fluid will flow overload or not follow the specification as the accuracy for every
reading will affect the record taken. All this will result in micro-fluidic channel flow
from the liquid that drive in from the syringe pump system. This problem occurred
due to the fluid drive from the syringe pump which the speed of motor affects the
fluids driving to the micro-fluidic.
1.4 Objectives of the project
The main objectives of this project are:
To design and fabricate a microfluidic mixer that performs serial dilutions
To develop an infusion pump with various flow rates of 0.5, 1 and 2 ml/min
To separate the concentration of fluid intensity
To produce four dilutions of two different liquids
Determine the efficiency of the dilution from various flow rates and speed
RPM
3
1.5 Project scopes
The following are the scope of project which is:
Using Comsol Multiphysics version 5.1 for modelling the microfluidic
simulation design
Programming software microcontroller to control the current driver to a
motorised linear slides.
Design model of infusion pump using Sketchup software.
Design model of microfluidic using AutoCAD
Using spectrophotometer to measure the light absorbance of colour intensity
4
CHAPTER 2
LITERATURE REVIEW
The literature review covered the past research related to the background of flow
mechanic for microfluidics and electronics of different liquid pump system. The
physics of microfluidic were reviewed and reported in this chapter. Surveying the
past literature review from a sources like journal, conference proceeding, articles and
dissertations with a purpose for collecting data that related to the work field research
progress development to avoid reinventing the research already conducted on the
topic.
2.1 Physics of microfluidic
2.1.1 Reynolds’s number
In microfluidic, laminar flow in the micro channel is very important to predict the
flow of droplet or particle in the fluid stream in function of fluid density, velocity,
pressure and fluid viscosity. Thus, The Reynolds number (Re) formula is used to
describe the parameter involve for the fluid flows in a microfluidic channel. The
Reynolds number can be calculated by using equation 2.1,
𝑅𝑒 =⍴𝜐L
µ (2.1)
in which ⍴ is the fluid density, 𝜐 is the velocity of fluid, µ is the dynamic viscosity and
L is the material characteristic length scale.
5
2.1.2 Fluidic resistance
Fluidic resistance occurred in the channels of both input and output stream is
governed by a set of equations whole solutions are well known [17]. The flow rate
presence within the micro channel given by formula of Q= ΔP/R, where Q is the
flow rate, ΔP is the pressure drop occurred across the channel, and R is the channel
resistance. Meanwhile, the resistance of a circular geometry can be calculated by the
formula of,
Figure 2.1: (a) Tube channel of microfluidic, (b) Formula used to calculate fluid resistance
From the Figure 2.1 as shown, the fluid resistance on the microfluidic channel as
shown in (a) calculated by using the formula on (b) where µ is the fluid viscosity, L
is the channel length, and r is the channel radius and R is the total resistance in the
tube channel.
2.1.3 Beer’s lambert law
In the spectrophotometer, the efficiency of the microfluidic mixer can be tested by
measuring the light absorption or spectroscopy of each light in different dilution.
Figure 2.2: (a) Absorption sample of concentration, (b) Beer’s lambert law formula
(b) (a)
(b) (a)
𝑹 =𝟖µ𝑳
𝝅𝒓𝟒
L
r
6
Figure 2.2 shows the relationship between absorption of concentration sample the
wavelength transmittance of liquid in the microfluidic channel as shown in (a) can be
accessed by beer’s lambert law (b) with the formula given by Absorbance = εLc. In
this equation, ε is the molar extinction coefficient, L is the path length of light passed
and c is the liquid concentration from the outlet stream of micro channel.
2.2 Fabrication of microfluidic
In this section, method of microfluidic fabrication discussed which there are two
process of microfluidic fabrication which ise photolithography and molding [6].
2.2.1 Photolithography
Photolithography is a process of photopatterning the channels of PDMS using a
mask. Generally, photoresist will be spin coated on a silicon wafer in compressed air.
Negative or positive masks will be placed on the photoresists and the silicon wafer
with the photoresist coating will be exposed to the UV light. The photo resist
exposed to the UV light will be softened and ready for wet etching process. The
etchant will etch the area without the pattern of the mask and leaving template of the
design behind on the silicon wafer in which, the template function as a mould.
Next is the step process of creating PDMS by using photolithography method. The
process started from (1) the resin spread on the on the flat surface such as petri dish
with desired thickness. For this PDMS, a 500 nm thickness is used. Next process is
(2) in which the resin spread on the flat surface undergo the UV exposition is
protected by the photomask applied to the resin with micro channel pattern.
Next, mould is developed in a solvent that etches the areas of resin that were not
exposed to UV light (3). The last step of photolithography (4) is the remove the
microfluidic pattern with the resin mould pattern from the photomask. The mould
then treated using silane to facilitate the microfluidic device as illustrated in Figure
2.3.
7
Figure 2.3: Photolithography process
2.2.2 Master molding process
Molding process is a common process used in the fabricating of microfluidic in
PDMS. It is used the silicone polymer based at ambient temperature to fabricate the
microfluidic. Molding commonly is a fabricating process after the photolithography
process is done.
Figure 2.4: Master mold process
The moulding process of PDMS is as shown in Figure 2.4. This figure indicates the
sequences process in which the first process producing microfluidic chips from the
8
mould by pouring the PDMS onto the mould. Then, an elastomer silicone gel and
curing agent poured to the mould and heated at high temperature. Next process is to
remove the hardened PDMS from the mould to obtain the micro-pattern of the
PDMS chip. Then, the process continued to create a hole for the input and output
channels of the microfluidic by using the holes puncher with size of 2 mm is
commonly used. Next, the PDMS and the glass slide were treated using plasma
treatment. This is allow for both of the microfluidic and glass slide can be bonded.
2.2.3 Advantages and disadvantages of PDMS
From the technological point of view in developing and fabricating of PDMS in,
there are some advantages and disadvantages measured from the intrinsic properties
which is:
Advantages of PDMS
i. Cheap.
ii. Biocompatible to all field in science or biological field application.
iii. It contain low auto fluorescence.
iv. PDMS can be replicate by using plasma treatment to formed sealed
microfluidic device.
Disadvantages of PDMS
i. PDMS can absorb small hydrophobic molecules especially in cell biology
application.
ii. Sensitive to expose with certain chemicals.
iii. Difficult to integrate with small electrode.
iv. Permeability of PDMS when exposed to water vapour that lead to evaporation
on the micro-channel.
9
2.3 Types of infusion syringe pump
2.3.1 Neonatal syringe pump
The neonatal syringe pump is used to deliver proper neonatal IV therapy accessible.
This device is capable to produce a flow rate between 5cc/hr to 40cc/hr for standard
syringe used with error produced within 15% and the delivery of intravenous
operation and volume at low infusion rates of (<20ml/hr) used by control the over
flow rates of the fluid flows through microfluidic channel. The prototype design were
tested for 20cc, 30cc, and 60cc syringes at room temperature (25𝑜 C). These systems
operate by driving the plunger of a syringe at controlled velocity to dispense fluids
through Intravenous (IV) channel [5].
Figure 2.1: Volume dispensed during two runs of 15cc/hr with a 20cc syringe pump [6]
Figure 2.5: (a) Novel mechanical syringe pump design and (b) Measurement result
The neonatal syringe pump prototyped as shown in the Figure 2.5 discussed the (a)
flow rate delivered data for two different runs of 5 cc and 40 cc to determines the
volume dispensed (ml) within 60 seconds and (b) shows the prototype design for the
syringe pump with a driving mass to drive the plunger of the syringe for delivery of
fluid purpose.
(a) (b)
Plunger
Syringe
Driving
mass
10
2.3.2 In-line gear pump
The experiment develops to determine the performance demonstrates a viable pump
to the syringe pumps for flowing fluid in micro-instrumentation by comparing the
first in-linear gear pump and second stage in-line gear pump [6]. The process of the
system to compare the flow rates of the flowing fluid from the syringe pump to the
different motor used in the experiment. One the pump used in the first experiment is
in-linear pump assemble at first stage demonstrated with 350 µl/min at 5000 rpm.
Other than that, when using fluid motor, the flow rates generates from the syringe
pump resulting of 200 ml/min at 4000 rpm [6].
Figure 2.6 (a): magnetic coupling structure of in-line gear pump [6]
Figure 2.6 (b): Flow rate versus pump rotation speed for theoretical and measurement in-line
gear pump [6]
11
2.3.3 Self-aligning gas or liquid micropump
In this section, a piezoelectric driven silicon membrane pump and passive dynamic
valve [7] developed to tolerant the relationship between the pump gases and liquid
with the gas bubble. The project development progress are used to reduce the dead
volume of fluid produced by the micropump thus increasing the compression ratio
from the gas pumping. The outcome of the project shows that the flow rate produced
a 1500 µl/𝑚𝑖𝑛−1 for liquid pump and 690 µl/𝑚𝑖𝑛−1 for gas pump.
Figure 2.7 (a): Measurement setup for Micropump illustration and (b) Measurement result
for the flow rate [7]
As shown in Figure 2.7, the setup for the micro-pump included the inlet and outlet
channel tube that connected between the micro-pump with a purpose to deliver the
fluid and the Perspex test jig is used to observe the presence of adhesive between the
inlet and outlet valve. Meanwhile for (b), it shows the result of measured pump rate
at zero backpressure over a frequency range between 0.5 KHz and 3.5 KHz. From
the result, the flow rate achieved at 1500 µl/𝑚𝑖𝑛−1 with frequency of 2.5 KHz.
Next, is the measurement setup discussed installation setup for the gas pump testing
with a water beaker included and the outlet valve placed 4 mm inside the water
beaker containing water. The setup proposed to measure the gas presence in the
beaker when the micropump started to infuse the fluid as illustrated in Figure 2.7 (c).
(a) (b)
12
Figure 2.7 (c): Measurement setup for gas pump [7]
Figure 2.7 (d): Measurement result for gas pump [7]
From the result as shown in the Figure 2.7 (d), the measurement for gas pump
repeated by 3 test with a result shows the gas started to pump at the frequency of 3.5
KHz. Thus, it resulting with approximate gas pump rate of 690 µl/min−1 at a
frequency of 3.4 kHz is calculated.
2.3.4 Micro-jet pump for microfluidic system
The developed pump system were used for sampling in microfluidic system under
gas actuation with the threshold gas actuation pressure of 2kPa at the initial and
increase to 42kPa during the suction process [8]. The architecture of the micro-jet
pump built with vacuum suction mode to decrease the air bubbles in the microfluidic
channel and also to overcome the interface tension between the liquid and solid wall
in the microfluidic system. The size dimension of the nozzle outlet is 100µm, width
of nozzle wall is 20 µm and depth of the micro-jet nozzle pump 80 µm and it is
fabricated by using one mask process.
13
Figure 2.8 (a): Image of micro-jet pump fabricated [8]
Figure 2.8 (b): Schematic diagram of micro-jet pump [8]
2.4 Micromixer dilution
Micro-dilution is an applications that widely used in the biological or science field
with a purpose of mixing a two or many different chemicals in a microfluidic device
through the channels built in the device. Applications such as reaction kinetics, rapid
crystallisation, drug delivery and nanoparticle synthesis. Micro-mixer designed for
millisecond or microsecond mixing by using fabrication method of PDMS. There are
two classification scheme of micro-mixer which is passive and active [9].
14
Figure 2.9: Classification scheme of micro-mixer [9]
2.4.1 Types of microfluidic mixer
(a) Single – target dilution microfluidic
Digital microfluidic (DMF) biochip [10,11] was used to developed a single-target
dilution by using several reagent with different concentration level for a dilution
process and mapping lab-bench protocol for an automate process. This process of
dilution used to minimizing the number of mix split-step of fluid and to minimize the
waste droplet during the automated sample preparation. The project also developed a
new dilution algorithm called Improved Dilution/Mixing Algorithm (IDMA) to
maximize the reuse of intermediate droplet generated during process.
Figure 2.10: Top and cross-sectional view of digital microfluidic (DMF) biochip [10]
15
(b) Digital microfluidic biochip
The project developed to design a chip and mapping lab-bench protocol [9] to carry
out dilution process of biochemical samples. Dilution/Mixing algorithm developed to
creation automation technique to reduce the production of waste droplets. The digital
microfluidic designed consists of two 0(n)-size rotary mixers and 0(n) storage
electrodes [10]. The droplet of fluids flows by applying the voltage control and
electrode adjacent at the same time. The patterns of control voltage varying the
merging, mixing and splitting of the biochemical droplet samples.
Figure 2.11: Schematic design of digital microfluidic biochip [11]
(c) Rectangular mixing channel
A method of mixing process in the micro-channel flows of microfluidic developed
measured and analysed the pressure during drive the fluid. Thus both of the two fluid
streams in pressure driven rectangular microfluidic channel [12]. Spectral method
were used in three dimensional equation to determine the non-uniform and uniform
mixing process for both fluids. The project carries out by analyse and measure the
mix of two fluids on silicon and poly (methyl methacrylate) (PMMA) based T-type
micro mixers.
Figure 2.12: Block diagram of setup for mixing pressure-driven microfluidic [12]
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(d) Vibrating micro-plate mixer
Mixing concept based on a vibrating micro-plate in microfluidic channel [13,14]
project developed to determine and to find the efficient mixing of solvent in
microfluidic. It done by decrease the diffusion path and increase the contact area
between fluids to be mixed. It used numerical investigation conducted by COMSOL
to determine the parameter of flow velocity, amplitude and frequency of vibrating
plate. Method used for this project by design two fluid streams with different
concentration flow into upper and down half of microfluidic channel. The channel
design with 250µm length and 50µm depth, meanwhile the micro-plate dimension is
20µm length and 5µm depth.
Figure 2.13: Channel of microfluidic geometry and operating parameter [13]
Figure 2.14: Channel of microfluidic design using COMSOL [13]
(e) Serial dilution micro-mixer
One of technique project developed to determine the estimation of microbial counts
obtained by using the serial dilution technique [14]. The techniques used to
investigate the microorganisms’ growth on bacteriological media and develop into
colony. The method used Agar plate to estimate the microbial counts of colony size
and plate area. The dilution ratios used from 2 to 100 ml and microbial counts
between 104 and 1012 microns of colony-forming units and 6.25 to 200 of size ratio
for plate size. This method proposed to shows the relative accuracy within ± 0.1
𝑙𝑜𝑔10 reading from computer simulations.
17
Figure 2.15: Graphical abstract for serial dilution experiments of microorganisms’ growth in
bacteriological [14]
(f) Straight, square wave and 3D serpentine micro-mixer
The other applications that used in microfluidic is mixing [13]. This project
developed to study about the computational of mixing a fluids in micro-channel to
define the mixing efficiency of fluid in straight, square-wave and three dimensional
(3D) serpentine micro-channels [1]. This project used COMSOL Multiphsyics [15]
to determine the velocity of fluids flow and use CATIA v6 software. To
characterized the mixing efficiency of fluids, this project used fluid concentration
from 0mol/𝑚3 and 50mol/𝑚3 with water and dilute with two different inlets in the
micro-channel.
Figure 2.16: 3 types of micro-channel used to determine the fluid velocity in micro-channel
[15]
Figure 2.16 shows the design of the micro-channel used to study about the
differences of mixing efficiency in the micro-channels. For experiment 1, then test
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was handled by using (a) straight micro-mixer, then the test repeated by using (b)
square wave micro-mixer and lastly (c) Serpentine micro-mixer.
(g) One channel micro-mixer
The project developed to studies about the fundamental concept of mixing fluids
with the microfluidic devices. The studies taking the consideration for the design of
the mixing application performances such as mixing index and residence time [16].
The gradient of the concentration of the species of fluid mixed called Fick’s Law
[17] defined to relate it with the proportional of flux to the gradient between two
reservoirs in the microfluidic devices to carry out the process of random motion for
fluid and the instantaneous state during the process.
Figure 2.17: Schematic of two input reservoir of microfluidic to mix two different fluid [16]
2.4.2 Applications of microfluidic mixers
From the previous literature review for the microfluidic mixers, the Table 2.1 shows
the summarization concluded from the previous literature review to define the
applications of various type the microfluidic mixer used in the microfluidic project.
Table 2.1: Applications of Microfluidic mixer used in the previous project developed
Types of Micromixer Application
i. Single – Target Dilution Microfluidic a) To minimize number of mix
split-step of fluid.
b) To minimize waste droplet.
c) Develop IDMA [9] algorithm to
maximize the reuse of
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intermediate droplet.
ii. Digital Microfluidic Biochip a) Dilution for biochemical droplet
sample.
b) To reduce the production of
waste droplet.
iii. Rectangular Mixing Channel a) Determine the non-uniform and
uniform mixing process.
b) Measure pressure of fluid in
channel.
iv. Vibrating Microplate Mixer a) Find the efficient mixing of
solvent in microfluidic with two
fluid streams with different
concentration flow into upper and
down half of microfluidic
channel.
v. Serial Dilution Micromixer a) To determine the estimation of
microbial counts obtained
b) Investigate the microorganisms’
growth on bacteriological media.
vi. Straight, Square – Wave & 3D
Serpentine
a) To define the mixing efficiency
of fluid
vii. One Channel Micromixer a) Define the mixing index and
residence time gradient of the
concentration of the fluid mixed
2.5 Comparison of previous projects
From the research done for the previous project done relate to the syringe pump and
microfluidic, this is important to make a conclusion from the literature review done
to compare the previous project done to collect some data for analysing.
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Table 2.2: Comparison of different syringe pump systems for use with microfluidic device
Associated Project Flow Rate Material Use Reference
i) Novel
Mechanical
Syringe Pump
i. Flow rate from
5cc/hr to 40cc/hr
i) electric motor
ii) Neonatal Syringe
Pump (NeoSyP)
iii) Syringe Plunger
Cynthia Sung et al.
2011 [5]
ii) In Line Gear
Pump
i) 350 µl/min at
5000 rpm
ii) 200 ml/min at
4000 rpm
i) Microfabricated
pump
ii) In-linear gear
pump
Andrew S.Dewa et
al. 1997 [6]
iii) Self-
Aligning/ Liquid
Micropump
i) 1500
µl/𝑚𝑖𝑛−1 for
liquid pump
ii) 690 µl/𝑚𝑖𝑛−1
for gas pump
i) Micropump
C.G.J Schabmuller
et al. 2002 [7]
iv) Micro-Jet Pump i) Pressure of
2kPa
i) Vacuum suction Xiuhan Li et al.
2006 [8]
As shown in Table 2.2 is the comparison of the differences between the associated
project by taking the flow rate reading of the fluid flow and materials from the
previous related to the infusion pump The pump developed which is neonatal syringe
pump, micro-fabricated pump, in-line gear pump, micro-pump and vacuum suction
pump were used during the project development on the previous project.
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Table 2.3: Comparison between project application techniques in microfluidic device
Associated
Project
Project Description Method References
i) Waste-aware
Single-target
Dilution of a
Biochemical
Fluid Using
Digital
Microfluidic
(DMF)
Biochips
i) Dilution process of
a biochemical by
using a digital
microfluidic (DMF)
biochips [9] and
mapping lab-bench
protocol for an
automate process.
i) Digital
microfluidic
(DMF) biochips
ii) Improved Dilution/
Mixing Algorithm
(IDMA)
Sudip Roy et al.
2015 [10,11]
ii) Analysis and
Measurement
of Mixing in
Pressure-
Driven
Microchannel
Flows
i) Determine the non-
uniform and
uniform mixing
process for both
fluids
ii) Analyse and
measure the mix of
two fluids on silicon
and poly (methyl
methacrylate)
(PMMA) based T-
type micro mixers
i) Spectral method 1. Jerry M. Chen et
al. 2006 [12]
iii) Simulation of a
Vibrating-Plate
based
Micromixer
i) To studies a mixing
concept based on a
vibrating microplate
in microfluidic
channel to achieve
an efficient mixing
i) COMSOL Software 1. Hongwei Sun et
al. 2006 [13]
iv) Estimation
Method for
i) To determine the
estimation of
i) Agar Plate used
from 2 to 100 ml
1. Avishai Ben-
David et al.
22
Serial Dilution
Experiments
microbial counts
obtained with the
serial dilution
technique
ii) The techniques to
investigate the
microorganisms’
growth on
bacteriological
media and develop
into colony
ii) Amicrobial counts
between 104 and
1012 microns of
colony-forming
units
iii) 6.25 to 200 of size
ratio for plate size
2014 [14]
v) Computational
Analysis for
Mixing of
Fluids Flowing
through Micro-
Channels of
Different
Geometries
i) To define the
mixing efficiency of
fluid in straight,
square-wave and
three dimensional
(3D) serpentine
micro-channels.
ii) Fluid concentration
from 0 mol/𝑚3 and
50 mol/𝑚3 with
water and dilute
with two different
inlets in the micro-
channel.
i) COMSOL software
ii) Catia v6 software
1. Sankha Shuvra
Das et al. 2014
[15]
vi) A Review on
Mixing in
Microfluidics
i) To studies about the
fundamental
concept of mixing
fluids with the
microfluidic devices
i) Using two reservoir
on microfluidic
technique
1. Yong Kweon
Suh et.al, 2010
[16]
23
As shown in Table 2.3 shows the few methods used for dilution and mixing the
chemical solution in the microfluidic channels. Based on the previous studies, the
microfluidic mixer basically used for cell culture, determine the mixed solution in
different channel design and etc. All the mixer used as a main application widely in
the biochemical studies.
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CHAPTER 3
METHODOLOGY
This chapter included the discussion on the design and simulation for the
microfluidic dilution device, the development of the infusion pump, and verification
of the performance of the infusion pump and the fabrication of the device. The flow
and pressure formed in the microfluidic mixer designed for dilution purpose was
studied in the Comsol Multiphysic version 5.1 software. While the infusion pump
was customised to provide suitable flow rates to achieve the four dilutions required
by the project. The calibration steps for the infusion pump to work together with the
microfluidic is required in order to prevent problems such as spillage and wastage of
fluid from the syringe while performing the desire functions. The design of the
microfluidic influenced the flow process when fluid was injected from the infusion
pump to the microfluidic device. Thus, the outcome of the project is to produce fluid
in different dilution concentrations at the output channel of the microfluidic mixer.
3.1 The flow chart of the project
In this part, the project progress was discussed for the related project development
progress for the simulation, fabrication and design of the microfluidic dilution and
infusion pump system.