micro fluidics
TRANSCRIPT
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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