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OVERVIEW OF MICROFLUIDICS
Heikki Koivo
Control Engineering Laboratory
Helsinki University of Technology
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Outline
1. Motivating examples
2. MEMS
3. Microfluidics/ Market situation
4. Microfluidic models
5. Microfluidic components
6. Microfluidic simulation
7. Applications of microfluidic devices
8. Future
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1. Motivating microfluidic
examples
Bio chips and beyond
Ink jet printers
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Bio chip
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Time,
November 8, 1999
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Time,
November 8, 1999
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Example of Gene chip by AFFYMETRIX
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Biochips
MANUAL SYSTEM
PCR
DISPENSER
INCUBATOR
CHIP CARRIER
BIOCHIP
PCR (Polymerase Chain Reaction)
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Biochip System
CHIP CARRIER
Dispenser Incubator Washer Reader
Plate robot
Array printer
Biochip imager
Biochip processing station
Biochip System
Dispenser Incubator Washer Reader
Plate robot
Biochip carrier
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Biochip System
Array printer
KEY FEATURES:
-from plate to chip/plate dispenser, 96, 384,
1536 well plates, slides
-50nl - 10l
-small dead volume
-separate tips in formatting use
-humidity controlled environment
BioRobotics
Cartesian
GeneMachines
Packard
Genome solutions
GeSim
Tecan
Genpack...
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Biochip System
KEY FEATURES:
-closed systems
Affymetrix
Caliper
Nanogen
Aclara
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What comes after genome chart?
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What comes after genome chart?
Proteomics and
beyond
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What comes after genome chart
wet brain research
Neural cells
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What comes after genome chart?
Terminator
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2. Ink jet printers
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Ink jet printer principle
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Ink jet printer principle
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Ink jet printers
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2. MICROELECTROMECHANICAL
SYSTEMS = MEMS
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Microsystems are well-known
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Microelectromechanical systems = MEMS
Components like sensors, actuators, electronics
integrated on a single chip
Sensors
Actuators
Signal processing
and control
Microsystem
Micro techniques
Micromechanics
Microelectronics
Micro-optics
Microfluidistics
Dimensions: 1 500 m
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What is not discussed,
but is very important
1. Microfabrication
2. Packaging
3. Energy and communications
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3. MICROFLUIDICS
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What is microfluidics?
Microfluidics refers to fluid flow in
microchannels as well as to microfluidic
devices (pumps, valves, mixers, etc.) and systems.
One of the dimensions of flow is measured in
m:s e.g. channel.
Microfluidics
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Why study microfluidics?
Reduction in size
Control of small amount of fluids
The reduced consumption of reagents
The capability of building integrated systems
Reduction of power consumption
Parallel devices + faster processes = high througput
Safety
Reliability
Integration + Multifunctionality
Portable devices
User friendly devices
Microfluidics Why study it?
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What to study in microfluidics?
Phenomena
Components
Systems
Applications
Microfluidics
TEKES funded survey project (2003)
http://butler.cc.tut.fi/~kuncova/MIFLUS/index.php
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Microfluidics - Scale
10
-10
10
-8
10
-6
10
-4
10
-2
10
0
10
2
nm m mm cm m km
10
-9
10
-7
10
-5
10
-3
10
-1
10
1
10
3
ions molecules macrom particles macropart
X-rays UV IR
wawes
RF
cells proteins
virus bacteria hair
smog smoke dust sand
mist/fog spray rain
die PCBs IC chip
nanotechnology precision engineering
conv. pumps chem. plants pumps & valves
conv. reactors reactors channel widths
MST
Adapted from A. van den Bergs lecture
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Market volume for MEMS products in 1996 and predictions for 2002*
1996 1996 2002 2002
Million units Million USD Million units Million USD
Product
Inkjet printer head 100 4 400 500 10 000
Chemical sensor 100 300 400 800
In vitro diagnostics 700 450 4 000 2 800
*Nexus study, also in
Microsystem Technology, Report by TEKES,1999
Market potential Existing products
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Market volume for emerging MEMS products from 1996 to 2002*
1996 1996 2002 2002
Million units Million USD Million units Million USD
Product
Drug delivery systems 1 10 100 1 000
Lab on a chip (DNA, etc) 0 0 100 1 000
Injection nozzles 10 10 30 500
Electric nose 0.001 0.1 0.05 5
*Nexus study, also in
Microsystem Technology, Report by TEKES,1999
Market potential - Emerging MEMS
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Genomics
Proteomics
Diagnostics
Basic research
Medical
research
Drug
development
Year
DNA Chip market
1999
$158
2001
$249
2005
$745
Bioinsights 2000
Year
$45
2000
$500
2005
Bioinsights 2001
Protein Chip market
Biochips
Biochips - market
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Biochips
Market prediction
Worldwide market for microarrays, arrayers, scanners
and microfluidics, through 2005
($ Millions)
2000 2005 AAGR %
2000-2005
Microarrays 225.9 535.8 18.9
Arrayers 51.4 86.6 11.0
Scanners 86.0 224.8 21.2
Microfluidics 34.0 219.8 45.2
Total 397.3 1067.0 21.8
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Biochips
Biochip applications
expression profiling
mutation screening, SNPs
sequencing
expression profiling
antibody screening:
specificity, cross-reactivity, epitope mapping
protein-protein interactions
protein- nucleic acid interactions (e.g. transcription
factors, transferases, regulatory sequences)
protein- drug interactions
assays of enzymatic activity:
post-translational modifications, substrate screening
Protein chips
DNA chips
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Microarray applications
Microarray market
Microarray market
Human
Diagnostics
Human
Diagnostics
Gene identification (P, D)
Gene identification (P, D)
Protein maps (P, D)
Protein maps (P, D)
Antibody production (P)
Antibody production (P)
Target ident. &
validation (D,P)
Target ident. &
validation (D,P)
Lead ident. &
validation (P,D)
Lead ident. &
validation (P,D)
Toxicity
studies (D,P)
Toxicity
studies (D,P)
Identification of
biomarkers (D, P)
Identification of
biomarkers (D, P)
Immuno-diagnostics (P)
Immuno-diagnostics (P)
Treatment & prognosis
(toxicity) (D,P)
Treatment & prognosis
(toxicity) (D,P) Protein
manufacture (P)
Protein
manufacture (P)
Pathogens: resistance,
mechanisms (D,P)
Pathogens: resistance,
mechanisms (D,P)
Pathogen: resistance,
mechanisms (P,D)
Pathogen: resistance,
mechanisms (P,D)
Control of breeding
and cloning (P,D)
Control of breeding
and cloning (P,D)
Food qualitity,
contaminations (P,D)
Food qualitity,
contaminations (P,D)
GMO in food (D)
GMO in food (D)
Pharmacogenomics/
proteomics
Pharmacogenomics/
proteomics
Mutation screening (D)
Mutation screening (D)
Pharma
Pharma
LSR/Biotech
LSR/Biotech
Agricultural/
Food Industry
Agricultural/
Food Industry
D = DNA arrays
P = protein arrays
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4. MICROFLUIDIC PHENOMENA
+ MODELS
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Continuity equation
( )
0, with = 1,2,3.
i
i
v
i
t x

+ =

Navier-Stokes equations
Isotropic Newtonian fluid
( ) 2
with , , = 1,2,3.
3
j
i i i k
j i j ij
j i j i k
v
v v v v p
v f v i j k
t x x xj x x x

(
| | | |

+ = + +
( | |
| |

(
\ . \ .

Boundary and initial conditions
Models for fluid flow
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Questions about microfluidics models!
Scaling?
Continuum Assumption?
Surface forces?
Other issues
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Scaling
1. In fluidics, assume two round pipes with the same flow situation, same
Reynolds number
Loss of pressure becomes much larger in microchannels (r small)
2. Required power
Required power becomes larger in microchannels (r small)
3. In microchannels Reynolds number tends to be small.
This implies laminarity of flow
1 1
2
1
, = constant p C C
r
=
2 2
1
, constant P C C
r
= =
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Continuum Assumption
In modeling fluid-flow, the actual molecular structure is
replaced by a continuum.
Knudsen number characterizes for gases.
Continuum hypothesis holds better for liquids than gases.
In microworld continuum assumption seems to hold reasonably
well. Breaks down in nanoworld. Need molecular dynamics.
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Continuum Assumption
Knudsen number characterizes gases no such thing for liquids.
Navier-Stokes applies when:
(1) When there are more than one million molecules in smallest
volume that a macroscopic change takes place.
(2) The flow is not too far from thermodynamic equilibrium.
Experimental evidence somewhat contradictory. Research needed.
In microworld continuum assumption seems to hold reasonably
well.
Breaks down in nanoworld. Need Molecular Dynamics.
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Surface forces
Van der Waals forces
Electrostatic forces
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Surface forces
A thin layer of liquid,
where electrical
potential separates
ions
The motion of ions
affects the properties
of liquid flow
EDL important in
channels with
diameter<1 mm
EDL=Electronic double layer
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Special phenomena in
microfluidics
Change in viscocity
Creation of turbulent flow
Compressability (especially in gas flow)
Slip flow (especially in gas flow)
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Laminar flow
Fluid particles move along smooth paths in laminas or layers
Turbulent flow
Fluid particles move in irregular paths, somewhat similar to
the molecular momentum transfer but on a much larger scale
Reynolds number
Laminar Re<2000 ; Turbulent Re>4000
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Knudsen number

mfp
= mean free path of molecules, D
h
=hydraulic
diameter
Measure for deviation of the state of the fluid
continuum
For K
n
<0.001 continuum
for K
n
>10 molecular flow
mfp
n
h
K
D

=
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Scaling effect
Surface forces and mass transfer
Start to dominate in sizes smaller than 1 mm
New phenomena arises because certain
surface forces are ignored in macro scale
Friction
Surface tension
Air bubbles
Liquid evaporation
Osmotic effects
Electrostatic forces
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Continuum assumption
Breakdown of continuum
assumption in gases
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5. MICROFLUIDIC COMPONENTS
Sensors
Actuators
Microfluidic systems
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Sensors
Pressure sensors
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Capacitive pressure sensors
Measures average
deflection
Properties (compared to
piezoresistive
counterparts):
higher pressure sensitivity
lower temperature sensitivity
more nonlinear
require larger die area and
more sophisticated sensing
circuitry
no hysteresis
better long-term stability
higher production costs
pressure
reference
capacitors
sensing
capacitors
Principle of a capacitive pressure sensor.
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Other types of pressure sensors
FISO Technologies:
fiber optic in-vivo pressure transducer,
diameter 0.5 mm
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Blood gas sensor
University of Neuchatel, Switzerland
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Flow sensors
Principles the same as in macroworld
Integrated Sensing Systems, Inc - 2003
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Microfluidic actuators
Actuators
Mixers
Microvalves
Micropumps
Fluid handling
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Mixer
Product of IMM
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Mixer
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Micropump
Product of IMM
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Microvalves
Examples of passive valves
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Microfluidic amplifier
HUT/TUT Finland
Tank
Piezoelectric actuator
Fluid
Bellows
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Micromanipulator uses microfluidic
amplifiers
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Microfluidics components
Microvalves
Microreactors
Microneedles
Microfilters
Microchips
Microheaters
Microdispensers
http://www.micronics.net/technologies/h_filter.php
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Microfluidic system
Chemical Analysis Systems
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Microfluidic system
Chemical Analysis Systems
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6. MICROFLUIDIC SIMULATION
Fluidic transport (component simulation)
Navier-Stokes equations
Finite difference methods
Finite Element Method (FEM)
Control volume method
Microscopic simulation
Molecular dynamics
Cellular automata
Microfluidic systems
Electrical analogues
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Microfluidic system
Simulation tools
CFX
Fluent/UNS
ANSYS
MEMCAD/ FLUMECAD
SPICE
APLAC
Hydraulic system simulation tools
ELMER
etc
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Microfluidic FEM simulation -
An example
Microchannel
CFX 4.2
(FEM) simulation
Pressure distribution
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Macroflow for system simulation
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Microfluidic systems
Lumped parameter electrical analogues
SUMMARY OF THROUGH AND ACROSS VARIABLES FOR PHYSICAL SYSTEMS
System Variable through Integrated trough Variable across Integrated across
element variable element variable
Electrical Current, i Charge, q Voltage Flux linkage,
difference, v
Fluid Fluid vol. flow, Q Volume, V Pressure Pressure
difference p momentum,
Thermal Heat flow, q Heat energy, H Temperature
difference, T
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Microfluidic
systems
Lumped parameter
electrical analogues
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Microfluidic system
Diffusor pump
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Current application areas
Analytical chemistry in medical applications ( bedside
auto-analyzers, disease detection, micro chemical analysis
system, etc)
Dosing in medical applications (drug delivery, etc)
Biotechnological applications (DNA analysis, etc)
Environmental applications (environmental monitoring,
etc)
Automotive applications (fluid delivery in engines, etc)
Electronic Applications (Ink-jet printers, local cooling, etc)
7. Applications of Microfluidic Devices
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Microfluidic network
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Field-effect electro-osmotic flow control
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Coupling cells to microelectronic devices
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Lab-on-a-chip
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Lab-on-a chip
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Lab-on-a-chip
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Principle of a capillory electrophoresis
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Microreactor Experiments in space
University of Neuchatel
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Fuel Cells
Professional Cameras, Service briefcases, Remote weather
monitoring stations, Variable message signs, Large Toys, Lanterns

100-300 W Medium
Lawn mowers, sweepers, scrubbers, wheelchairs, Industrial Power
Tools, Portable Power Supply (Backup/emergency power, camping,
),
> 500 W Large
Mobile phones, Hearing Aids, Clocks, Watches, Pagers, PDA,
Small Toys, Audio, Cameras (Photo or Digital), Medical
< 5 W Micro
Laptops, Camcorders, Toys, Portable Tools, Military applications

5-50 W Small
Potential Applications Description Portable Type
Portable Fuel Cells have a wide range of potential portable applications
similar to secondary batteries in the micro to medium power segments.
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Direct Methanol Fuel Cell (DMFC)
Source: Fuel Cell Technology Handbook, Gregor Hoogers, CRC Press 2003
CH3OH + H2O CO2 + 6H+ + 6e-
Eo = 0.046 V
(electro-oxidation of methanol)
Driven Load
Anode Cathode
Methanol + Water
Carbon Dioxide
Anode
Diffusion
Media
Anode
Catalyst
Layer
e- e-
H+
H+
H+
Oxygen
Water
Acidic Electrolyte
Solid Polymer
Electrolyte: PEM
(Proton Exchange
Membrane)
Cathode
Catalyst
Layer
Cathode Diffusion
Media
3/2O2 + 6H+ + 6e- 3H2O
Eo = 1.23 V
Overall Reaction
CH3OH + 3/2O2 +H2O CO2 + 3H2O
Ecell = 1.18 V
Acidic electrolytes are
usually more advantageous
to aid CO2 rejection since
insoluble carbonates form
in alkaline electrolytes
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Fuel Cells
Technical Challenges for DMFC
A simplified electrochemical system but still need peripherals to operate properly
increasing the overall cells weight Difficult to miniaturize?
Fuel production
& delivery
Microfluidics Electronics
Fuel Cell
Core
Fuel
Cell
Core
MEA
Fuel
Delivery
System
H2 Production
System
Energy Recovery System
Air Circulation System
Water Recovery
& Circulation
Sensors Pumps
Control Circuitry
Control
Circuitry
DC/DC
Converter
Battery
Direct Methanol Fuel Cell (DMFC)
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Fuel Cell Motorola (K.L. Davis)
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Fuel Cell Motorola
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Cooling for cellular phone
H. Hashemi & A. Langari
Electronics Cooling, May 2000
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Cooling for cellular phone
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Cooling for cellular phone
ANSYS simulation
Temperature distribution in GaAs device
Temperature distribution in package
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Cooling for cellular phone
Comparison between original and enhanced design
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MICROFLUIDICS
Consumer Electronics
MICROFLUIDICS MICROFLUIDICS
Consumer Electronics Consumer Electronics
Local cooling Inkjet printing
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New Jarvik artificial heart
only a size of a thumb
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Market
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Market
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MEMS will be allover, like plastic. They are vital. They
will infiltrate everything, Karen Markus- Director of the
MEMS program at MCNC Science, October 1998.
We are approaching another revolution that will rival
the Industrial Revolution of the 18
th
century, Takayuki
Hirano Director of Japans Micromachine Center
TIME, December 1996
We believe that MEMS will revolutionize the way people
build products in the 21
st
century by coupling compu-
tation to the physical world on a scale that has never
before been possible, Xerox Palo Alto Research Center
8. Future of MEMS
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Time,
November 8, 1999
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Some books that discuss microfluidics
1. S. Fatikow, U. Rembold: Microsystem Technology and
Microrobotics, Springer, 1997.
2. M. Madou: Fundamentals of Microfabrication, CRC,
1997.
3. A. Nathan and H. Baltes: Microtransducer CAD, Physical
and Computational Aspects, Springer, 1999
4. B. Romanowicz: Methodology for the Modeling and
Simulation of Microsystems, Kluwer, 1998.
5. S. Senturia: Microsystem design, Kluwer, 2000.
6. MEMS Handbook, (Ed. M. Gad-El-Hak, Kluwer, 2002.
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Thanks
To my research staff in microsystems both
at
Helsinki University of Technology and
Tampere University of Technolgy
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Issues from control point of view
Modelling, especially systems
Simulation
Control of issues in microworld (actuators)
Adhesion
Hysteresis
Control of large (number) of really
distributed systems
Communication, Energy