micro fluidics

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OVERVIEW OF MICROFLUIDICS

Heikki KoivoControl Engineering Laboratory

Helsinki University of Technology

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Outline

1. Motivating examples2. MEMS3. Microfluidics/ Market situation4. Microfluidic models5. Microfluidic components6. Microfluidic simulation7. Applications of microfluidic devices8. 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

INCUBATORCHIP 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 - 10µl-small dead volume-separate tips in formatting use-humidity controlled environment

BioRoboticsCartesianGeneMachinesPackardGenome solutionsGeSimTecanGenpack...

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Biochip System

KEY FEATURES:

-closed systems

AffymetrixCaliperNanogenAclara

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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 processingand control

Microsystem

Micro techniques• Micromechanics• Microelectronics• Micro-optics• Microfluidistics

Dimensions: 1 – 500 µm

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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 µm: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 10-2 100 102

Å nm µm mm cm m km

10-9 10-7 10-5 10-3 10-1 101 103

ions molecules macrom µparticles macropart

X-rays UV IR µwawes RF

cells proteins

virus bacteria hair

smog smoke dust sand

mist/fog spray rain

die PCBsIC chip

nanotechnology precision engineering

conv. pumps chem. plants µpumps & valves

conv. reactors µreactors µchannel widths

MST

Adapted from A. van den Berg’s lecture

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

ProductInkjet 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 inMicrosystem 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 2002Million units Million USD Million units Million USD

ProductDrug 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 inMicrosystem Technology, Report by TEKES,1999

Market potential - Emerging MEMS

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Genomics

Proteomics

Diagnostics

Basic research

Medicalresearch

Drug development

Year

DNA Chip market

1999

$158

2001

$249

2005

$745

Bioinsights 2000

Year

$45

2000

$500

2005

Bioinsights 2001

Protein Chip market

BiochipsBiochips - market

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BiochipsMarket 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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BiochipsBiochip 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 marketMicroarray 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)

PharmaPharma LSR/BiotechLSR/BiotechAgricultural/

Food IndustryAgricultural/

Food Industry

D = DNA arraysP = protein arrays

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4. MICROFLUIDIC PHENOMENA + MODELS

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Continuity equation

( )0, with = 1,2,3.i

i

v it x

ρρ ∂∂+ =

∂ ∂

Navier-Stokes equations

Isotropic Newtonian fluid

( ) 2 with , , = 1,2,3.

3ji i i k

j i j ijj i j i k

vv v v vpv f v i j kt x x xj x x x

ρ µ δ ∂∂ ∂ ∂ ∂∂ ∂

+ = − + + − ∂ ∂ ∂ ∂ ∂ ∂ ∂

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 Reynold’s number tends to be small.This implies laminarity of flow

1 12

1, = constantp C C

r∆ =

2 2

1, constantP 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 mmEDL=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

λmfp = 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

mfpn

h

KDλ

=

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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

MicroheatersMicrodispensers

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

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Microfluidic systemChemical Analysis Systems

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Microfluidic systemChemical 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 acrosselement variable element variable

Electrical Current, i Charge, q Voltage Flux linkage, λdifference, v

Fluid Fluid vol. flow, Q Volume, V Pressure Pressuredifference ∆p momentum, γ

Thermal Heat flow, q Heat energy, H Temperaturedifference, ∆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 WMedium

Lawn mowers, sweepers, scrubbers, wheelchairs, Industrial Power Tools, Portable Power Supply (Backup/emergency power, camping, …), …

> 500 WLarge

Mobile phones, Hearing Aids, Clocks, Watches, Pagers, PDA, Small Toys, Audio, Cameras (Photo or Digital), Medical …

< 5 WMicro

Laptops, Camcorders, Toys, Portable Tools, Military applications…

5-50 WSmall

Potential ApplicationsDescriptionPortable Type

Portable Fuel Cells have a wide range of potential portable applicationssimilar 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 LoadAnode Cathode

Methanol + Water

Carbon Dioxide

Anode Diffusion Media

Anode Catalyst Layer

e- e-

H+

H+

H+

Oxygen

Water

Acidic ElectrolyteSolid Polymer Electrolyte: PEM (Proton Exchange Membrane)

Cathode Catalyst Layer

Cathode Diffusion Media

3/2O2 + 6H+ + 6e- 3H2OEo = 1.23 V

Overall Reaction

CH3OH + 3/2O2 +H2O CO2 + 3H2OEcell = 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 CellsTechnical Challenges for DMFC

A simplified electrochemical system but still need peripherals to operate properly increasing the overall cell’s weight Difficult to miniaturize?

Fuel production & delivery

Microfluidics ElectronicsFuel Cell

Core

Fuel Cell Core MEA

Fuel Delivery System

H2 ProductionSystem

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. LangariElectronics 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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MICROFLUIDICSConsumer Electronics

MICROFLUIDICSMICROFLUIDICSConsumer ElectronicsConsumer Electronics

Local cooling Inkjet printing

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New Jarvik artificial heartonly 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 18th century,” Takayuki Hirano – Director of Japan’s Micromachine Center –TIME, December 1996

”We believe that MEMS will revolutionize the way people build products in the 21st 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 systemsSimulationControl of issues in microworld (actuators)

AdhesionHysteresis

Control of large (number) of really distributed systemsCommunication, Energy