OVERVIEW OF MICROFLUIDICS

Heikki Koivo
Control Engineering Laboratory
Helsinki University of Technology

Outline
1.
2.
3.
4.
5.
6.
7.
8.

Motivating examples
MEMS
Microfluidics/ Market situation
Microfluidic models
Microfluidic components
Microfluidic simulation
Applications of microfluidic devices
Future
2

1. Motivating microfluidic
examples

Bio chips and beyond

Ink jet printers

Bio chip

Time,
November 8, 1999

Time,
November 8, 1999

Example of Gene chip by AFFYMETRIX

Biochips
BIOCHIP

MANUAL SYSTEM

DISPENSER

PCR
PCR (Polymerase Chain Reaction)
INCUBATOR

CHIP CARRIER

Biochip System

Array printer
Biochip processing station
Biochip carrier
Biochip imager
Plate robot

Dispenser Incubator

Washer

Reader

CHIP CARRIER

Biochip System
10

Biochip System
KEY FEATURES:

Array printer

-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...
11

Biochip System
KEY FEATURES:
-closed systems

Affymetrix
Caliper
Nanogen
Aclara

12

What comes after genome chart?

13

What comes after genome chart?

Proteomics and
beyond

14

What comes after genome chart

wet brain research

Neural cells

15

What comes after genome chart?

Terminator

16

2. Ink jet printers

17

Ink jet printer principle

18

Ink jet printer principle

19

Ink jet printers

20

2. MICROELECTROMECHANICAL
SYSTEMS = MEMS

21

Microsystems are well-known

22

Microelectromechanical systems = MEMS

Components like sensors, actuators, electronics
integrated on a single chip
Sensors

Micro techniques
Micromechanics

Actuators

Microelectronics
Micro-optics
Microfluidistics

Microsystem

Signal processing
and control

Dimensions: 1 500 m

23

What is not discussed,

but is very important
1. Microfabrication
2. Packaging
3. Energy and communications

24

3. MICROFLUIDICS

25

Microfluidics

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.
26

Microfluidics Why study it?

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
27

Microfluidics
What

to study in microfluidics?

Phenomena

Components

Systems

Applications

TEKES funded survey project (2003)

http://butler.cc.tut.fi/~kuncova/MIFLUS/index.php
28

Microfluidics - Scale
MST
nanotechnology

precision engineering
pumps & valves
channel widths

conv. pumps

reactors

chem. plants

conv. reactors

die IC chip PCBs

X-rays

UV
mist/fog
smog

10-10

rain
sand

hair

macrom particles

macropart

m
10-8

RF

cells

nm
10-9

dust
bacteria

proteins
molecules

spray

smoke

virus

ions

wawes

IR

10-7

10-6

10-5

10-4

mm

cm

10-3

10-2

m
10-1

100

km
101

102
29

Adapted from A. van den Bergs lecture

Market potential Existing products

Market volume for MEMS products in 1996 and predictions for 2002*
1996
Million units

1996
Million USD

2002
Million units

2002
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
30

103

Market potential - Emerging MEMS

Market volume for emerging MEMS products from 1996 to 2002*
1996
Million units

1996
Million USD

2002
Million units

2002
Million USD

Product
Drug delivery systems

10

100

1 000

Lab on a chip (DNA, etc)

100

1 000

Injection nozzles

10

10

30

500

Electric nose

0.001

0.1

0.05

*Nexus study, also in

Microsystem Technology, Report by TEKES,1999
31

Biochips
Biochips
- market
Basic research
Medical
research

Proteomics

Drug
development Diagnostics
Genomics

DNA Chip market

Year

1999

2001

2005

$158

$249

$745

Bioinsights 2000

Protein Chip market

Year

2000

2005

$45

$500
Bioinsights 2001
32

Biochips
Market
prediction
Worldwide market for microarrays, arrayers, scanners
and microfluidics, through 2005
($ Millions)
2000

2005

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

397.3

1067.0

21.8

Microarrays

Total

AAGR %
2000-2005

33

BiochipBiochips
applications
DNA chips

expression profiling
mutation screening, SNPs
sequencing
expression profiling

Protein chips

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
34

Microarray applications
Microarray
Microarraymarket
market

Pharma
Pharma

Target
Targetident.
ident.&&
validation
validation(D,P)
(D,P)
Pharmacogenomics/
Pharmacogenomics/
proteomics
proteomics
Lead ident. &
Lead ident. &
validation (P,D)
validation (P,D)
Toxicity
Toxicity
studies (D,P)
studies (D,P)

Human
Human
Diagnostics
Diagnostics

LSR/Biotech
LSR/Biotech

Identification
Identificationofof
biomarkers
biomarkers(D,
(D,P)P)

Gene
Geneidentification
identification(P,
(P,D)
D)

Mutation screening (D)

Mutation screening (D)
Immuno-diagnostics (P)
Immuno-diagnostics (P)
Treatment
Treatment&&prognosis
prognosis
(toxicity)
(toxicity)(D,P)
(D,P)
Pathogens: resistance,
Pathogens: resistance,
mechanisms (D,P)
mechanisms (D,P)

Protein maps (P, D)

Protein maps (P, D)

Antibody production (P)

Antibody production (P)
Protein
Protein
manufacture (P)
manufacture (P)

Agricultural/
Agricultural/
Food
FoodIndustry
Industry
Pathogen:
Pathogen:resistance,
resistance,
mechanisms
mechanisms(P,D)
(P,D)

Food
Foodqualitity,
qualitity,
contaminations
contaminations(P,D)
(P,D)
GMO in food (D)
GMO in food (D)

Control of breeding
Control of breeding
and cloning (P,D)
and cloning (P,D)
D = DNA arrays 35
P = protein arrays

4. MICROFLUIDIC PHENOMENA
+ MODELS

36

Models for fluid flow

Continuity equation
( vi )
+
= 0, with i = 1,2,3.
t
xi

Navier-Stokes equations
vi
v 2 v
(vi )
p
vi

f
+ vj
=

+
+ v j j ij k

i
t
x j
xi xj x j
xi 3 xk

with i, j , k = 1,2,3.

Boundary and initial conditions

Isotropic Newtonian fluid

37

Questions about microfluidics models!

Scaling?
Continuum Assumption?
Surface forces?
Other issues

38

Scaling
1.

In fluidics, assume two round pipes with the same flow situation, same
Reynolds number

p = C1

1
, C1 = constant
r2

Loss of pressure becomes much larger in microchannels (r small)

2.

Required power
1
P = C2 , C2 = constant
r

Required power becomes larger in microchannels (r small)

3.

In microchannels Reynolds number tends to be small.

This implies laminarity of flow
39

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.
40

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.
41

Surface forces

Van der Waals forces

Electrostatic forces

42

Surface forces

EDL=Electronic double layer

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
43

Special phenomena in
microfluidics

Change in viscocity
Creation of turbulent flow
Compressability (especially in gas flow)
Slip flow (especially in gas flow)

44

 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

45

Knudsen number

Kn =

mfp
Dh

mfp = mean free path of molecules, Dh=hydraulic

diameter
Measure for deviation of the state of the fluid
continuum
For Kn<0.001 continuum
for Kn>10 molecular flow
46

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
47

Continuum assumption
Breakdown of continuum
assumption in gases

48

5. MICROFLUIDIC COMPONENTS
Sensors
Actuators
Microfluidic systems

49

Sensors
Pressure sensors

50

Capacitive pressure sensors

reference
capacitors

sensing
capacitors

pressure
Principle of a capacitive pressure sensor.

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
51

Other types of pressure sensors

FISO Technologies:
fiber optic in-vivo pressure transducer,
diameter 0.5 mm

52

Blood gas sensor

University of Neuchatel, Switzerland

53

Flow sensors
Principles the same as in macroworld

Integrated Sensing Systems, Inc - 2003

54

Microfluidic actuators
Actuators
Mixers
Microvalves
Micropumps
Fluid handling

55

Mixer

Product of IMM

56

Mixer

57

Micropump

Product of IMM

58

Microvalves
Examples of passive valves

59

Microfluidic amplifier
Fluid

Piezoelectric actuator

Bellows

Tank

HUT/TUT Finland

60

Micromanipulator uses microfluidic

amplifiers

61

Microfluidics components

Microchips
Microvalves
Microreactors

Microneedles
Microfilters

Microdispensers

Microheaters

http://www.micronics.net/technologies/h_filter.php

62

Microfluidic system
Chemical Analysis Systems

63

Microfluidic system
Chemical Analysis Systems

64

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
65

Microfluidic system
Simulation tools

CFX
Fluent/UNS
ANSYS
MEMCAD/ FLUMECAD
SPICE
APLAC
Hydraulic system simulation tools
ELMER
etc
66

Microfluidic FEM simulation An example

Microchannel
CFX 4.2
(FEM) simulation
Pressure distribution

67

Macroflow for system simulation

68

Microfluidic systems
Lumped parameter electrical analogues
SUMMARY OF THROUGH AND ACROSS VARIABLES FOR PHYSICAL SYSTEMS
System Variable through Integrated trough
element
variable

Variable across
element

Integrated across
variable

Electrical Current, i

Charge, q

Voltage
difference, v

Flux linkage,

Volume, V

Pressure
difference p

Pressure
momentum,

Heat energy, H

Temperature
difference, T

Fluid

Fluid vol. flow, Q

Thermal Heat flow, q

69

Microfluidic
systems
Lumped parameter
electrical analogues

70

Microfluidic system
Diffusor pump

71

7. Applications of Microfluidic Devices

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,72etc)

Microfluidic network

73

Field-effect electro-osmotic flow control

74

Coupling cells to microelectronic devices

75

Lab-on-a-chip

76

Lab-on-a chip

77

Lab-on-a-chip

78

79

Principle of a capillory electrophoresis

80

81

Microreactor Experiments in space

University of Neuchatel

82

Fuel Cells
Portable Fuel Cells have a wide range of potential portable applications
similar to secondary batteries in the micro to medium power segments.
Portable Type

Description

Potential Applications

Micro

<5W

Mobile phones, Hearing Aids, Clocks, Watches, Pagers, PDA,

Small Toys, Audio, Cameras (Photo or Digital), Medical

Small

5-50 W

Laptops, Camcorders, Toys, Portable Tools, Military applications

Medium

100-300 W

Professional Cameras, Service briefcases, Remote weather

monitoring stations, Variable message signs, Large Toys, Lanterns

Large

> 500 W

Lawn mowers, sweepers, scrubbers, wheelchairs, Industrial Power

Tools, Portable Power Supply (Backup/emergency power, camping,
),
83

Direct Methanol Fuel Cell (DMFC)

Overall Reaction
CH3OH + 3/2O2 +H2O CO2 + 3H2O
Ecell = 1.18 V

Anode
CH3OH + H2O CO2 + 6H+ + 6eEo = 0.046 V
(electro-oxidation of methanol)

Driven Load

e-

Cathode

e-

3/2O2 + 6H+ + 6e- 3H2O

Eo = 1.23 V

H+
Oxygen

Carbon Dioxide

H+
Methanol + Water
Anode
Diffusion
Media

H+
Anode
Acidic Electrolyte
Catalyst
Solid Polymer
Layer
Electrolyte: PEM
(Proton Exchange
Membrane)

Source: Fuel Cell Technology Handbook, Gregor Hoogers, CRC Press 2003

Water
Cathode Diffusion
Media
Cathode
Catalyst
Layer

Acidic electrolytes are

usually more advantageous
to aid CO2 rejection since
insoluble carbonates form
in alkaline electrolytes
84

Fuel Cells
Technical Challenges for DMFC
z

A simplified electrochemical system but still need peripherals to operate properly

increasing the overall cells weight Difficult to miniaturize?
Water Recovery
& Circulation

Control
Circuitry

Energy Recovery System

H2 Production
System

Fuel
Delivery
System

Air Circulation System

Sensors

Pumps

Fuel
Cell
Core
MEA

DC/DC
Converter

Battery

Control Circuitry

Fuel production
& delivery

Microfluidics

Fuel Cell
Core

Electronics

Direct Methanol Fuel Cell (DMFC)

85

Fuel Cell Motorola (K.L. Davis)

86

Fuel Cell Motorola

87

Cooling for cellular phone

H. Hashemi & A. Langari

Electronics Cooling, May 2000

88

Cooling for cellular phone

89

Cooling for cellular phone

Temperature distribution in package

ANSYS simulation
Temperature distribution in GaAs90device

Cooling for cellular phone

Comparison between original and enhanced design

91

92

MICROFLUIDICS
Consumer Electronics
Local cooling

Inkjet printing

93

New Jarvik artificial heart

only a size of a thumb

94

Market

95

Market

96

8. Future of MEMS
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 18th century, Takayuki
Hirano Director of Japans Micromachine Center
TIME, December 1996
We believe that MEMS will revolutionize the way people
build products in the 21st century by coupling computation to the physical world on a scale that has never
before been possible, Xerox Palo Alto Research Center
97

Time,
November 8, 1999

98

Some books that discuss microfluidics

1.
2.
3.
4.
5.
6.

S. Fatikow, U. Rembold: Microsystem Technology and

Microrobotics, Springer, 1997.
M. Madou: Fundamentals of Microfabrication, CRC,
1997.
A. Nathan and H. Baltes: Microtransducer CAD, Physical
and Computational Aspects, Springer, 1999
B. Romanowicz: Methodology for the Modeling and
Simulation of Microsystems, Kluwer, 1998.
S. Senturia: Microsystem design, Kluwer, 2000.
MEMS Handbook, (Ed. M. Gad-El-Hak, Kluwer, 2002.

99

Thanks
To my research staff in microsystems both
at
Helsinki University of Technology and
Tampere University of Technolgy

100

101

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
102