Microsystems in Biomedical Engineering
2004
by
Oddvar Søråsen
Department of Informatics, UiO
23. March, 2004
Microsystems in Biomedical Engineering
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“Swiss Foundation for Research in Microtechnology”
EPFL, Lausanne, 10 - 11 March, 2004
Focus: Miniaturization of devices useful in biomedical
engineering
Micromachining and MEMS technologies
are powerful tools!
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Material from course by FSRM
Contents
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Definitions
Technology and principles
Applications
Benefits
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Terms
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MEMS (Microelectromechanical systems)
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Miniaturization of electrical, mechanical, optical, fluidic, magnetic
systems
Microtechnology (e.g. MRL)
Microsystems (Europe), MST
Micromachines (Asia)
“Biomicrotechnology”
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Wide and highly dynamic field
Many different technologies
Typical: biomolecules/cells will be combined with technical
structures
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“Biomedical” applications
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Second largest application area for MEMS after
automotive
Challenge: identify niches with sufficient market
potential to justify the long and expensive development
process
Forecast: MEMS-enabled chemical sensing and
microfluidic systems will grow tremendously!
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Technology
Microfabrication: batch processing from IC -> expanded
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Photolithography
Bulk micromachining
Surface micromachining (sacrificial + structural layers)
Silicon, a central material:
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+ mechanical properties (stress – strain, “spenning – tøyning”),
+ excellent piezoresistive material
- optical penetration
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Non-silicon microfabrication
Metal (electroplating)
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Used directly or as mould (plastic) (Ni, Cu, Au)
Laser (cutting, removing glass, plastics, ceramics)
Glass microstructures
Plastic microstructures (laminate)
Hybrid microstructures
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Hewlett Packard Inkjet Nozzle Roadmap
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MEMS structures and principles
Pressure sensors
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Inertial sensors (accelerometers and gyros)
Detection mechanisms:
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bending of beams, diaphragm
piezoresistive elements, capacitive detection
Fluidic systems
Actuators (mirror deflection)
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Applications in Biomedical Engineering
In Vivo systems (contact with patient bodies)
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A. Electrical stimulation
B. Biosensors
C. MIS Minimally invasive surgery
In Vitro systems (clinical settings)
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Medical diagnostics
R&D in drug discovery and development
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A. In Vivo: electrical stimulation
Neurostimulators in the cardiovascular area
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Pacemaker, defibrillator (flagships, most mature)
All the main heart disorders are being treated with
microelectronic implants!
Future: Rate-responsive pacemaker (accelerometers,
pressure/flow sensors)
Coclear implants (Otology)
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Commercialized
Widespread use in children with profound deafness.
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A. In Vivo: electrical stimulation, cont.
Retinal implants (futuristic) (Ophthalmology)
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Visual systems to the blind
Epiretinal implant device: Optobionics
FES functional electrical stimulation
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Bone growth stimulator
Bladder stimulators (small market yet)
Restoring movements to paraplegics (lammet fra livet og ned)
and stroke victims (not in commercialization yet)
Dropped foot syndrome. Attaching electrodes to special nerve
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Neurology and rehabilitation
Limb function restoration
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Sensors for prosthetic devices
Freehand system from NeuroControl Corp
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approved FDA in 1997 for quadriplegics (can use their
shoulder and upper arm, but not their hands)
Implanted in the chest - 8 electrodes
Can grip lightweight objects
Telemetry
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RF MEMS, inductive coupling
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Neural-electronic interfaces
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Micromachined neural sensors and stimulators
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many electrodes co-fabricated
tailor systems to the dimensions of individual cells
Blocking brain signals that cause tremor (Parkinson)
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Medtronic
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control prosthetic limbs with signals from the brain or spinal
column
MEMS:
Drug delivery
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Asthma, attack prevention
Implantable drug infusion pumps (1980- to cancer pat.)
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Small pump controlled by an electronic module
Biotelemetry unit, lithium battery
Refillable reservoir, catheter delivers drug where needed
Advantages: preprograming, versatile regulation, adapted to
patient needs, patient compliance (tilpasning), lower risk of
infection, delivery to targeted internal sites, reduced doses and
side effects
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Aeorosol
Technology Analysis: Drug Delivery
STEAG microParts, Germany
Boehringer Ingelheim Pharma GmbH & Co. KG
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ÂBoehringer Ingelheim (D)
ÂSTEAG microParts (D)
Nebulisers for drug inhalers
Technology Analysis: Drug Delivery
Debiotech Chip
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Technology Analysis: Drug Delivery
Debiotech Chip
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Source: Debiotech
Patches, stents
Transdermal patch systems
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For transcutaneous delivery of drugs
(“passing, entering, or by penetration through the skin”)
Electrophoresis are used
At an advanced clinical trial stage
Stents!
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B. In Vivo: biosensors
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Sensors typically measure physical rather than
biochemical parameters
Pressure sensors inserted into a catheter and inserted
into arteries (blood, bladder, cerebral spinal pressure)
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Blood pressure sensors used during surgery
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measuring intravascular blood pressure
Brain pressure
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Highly invasive brain surgery
Patient still conscious
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Implanted sensor: sown in place, light communication
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Radi Catheter
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Probe placement is
facilitated by two depth
markers located at
35 and 40 cm.
Technology Analysis: Monitoring & P.O.C
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B. Biosensors, cont.
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Catheters (RADI) and endoscopes
Ultrasound blood pressure
Gasteroentology: Swallowable camera
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Imaging Ltd, Israel
CMOS image sensors, ASIC, LED illumination, video
telemetry, UHF radiotelemetry up to 5 hours (small intestine)
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Technology Analysis: Catheters & Endoscopes
Given Imaging – Imaging System in a Pill
Pill - 11mm diameter 27mm long
Wireless link
Wired link
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Optical lens
Battery Radio
and CMOS
transmitter
imager
Source; Given Imaging Ltd
B. Biosensors, cont.
Diabetes
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Large activity
Commercial product:
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GlucoWatch from Cygnus, CGMS sensor system
Spectroscopy used
No in vivo sensors in common use for monitoring
metabolics
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due to sensor drift, perturbation of the surrounding tissue
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The glucose-monitoring watch. Cross-section, top left. Comparison of prototype
1 COB and prototype 2 SMD board, top right. Prototype 1 final device, bottom
left. Pre-series device, bottom right.
C. MIS Minimally Invasive Surgery
“Keyhole surgery”
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Toolbox:
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Micromanipulators
Miniaturized surgical microinstruments
Micropump, microvalves, microfilters, microneedles,
microsyringes (sprøyter), incredibly sharp blades
Pressure monitors are used
Catheters with imaging capabilities, incl. ultrasonic
probes
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In Vitro devices: Biochips
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Miniaturize entire biomedical systems
Microfluidic systems typically have
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Smaller volume, reduction of system size
Precise control of sample volume
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thermal, fluidic
Massively parallel tests
Possible reduction in system cost
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In Vitro: Main technologies
Lab-on-chip devices
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Integrate different biochemical laboratory processes on a
single chip
Microarrays
Application areas:
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Monitoring: blood pressure, glucose, blood gas ++
Life science research and drug discovery
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Technology Analysis:Glass Microreactors
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Lab-on-chip
Blood analysis at the bedside (“point-of-care” testing)
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Systems are microfluidic based
Tiny channels etched in the chip, glass, plastic
Transport of droplets of fluid by electrophoreses
Tiny pumps and valves in some cases
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- most without moving parts
CD (centrifugal force), SAW
Single use chip (HP and iSTAT), 2 min, 2-3 drops
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iSTAT
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• blood analysis
glucose, urea, pH, blood gases,
• portable POC device
• analyser + disposable cartridges
• microfluidic channels
• micro-fabricated thin-film electrodes
iSTAT Sensor Chips
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Microarrays
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Integrate a high number of identical types of reactions on
a single chip (two-dim)
Discrete areas containing biomolecules that are
capable of interacting specifically with a complementary
molecule
Can determine which component is present in a
speciman
Optical detection of pattern
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Microsystems for genetic analysis
Gene chips
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DNA analysis
Calipher DNA analysis plate
Fragment of genome is identified on a chip surface
DNA amplification
Protein chips
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Different proteines or peptides are identified
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Glass Microstructures Example
Caliper DNA Analysis Plate
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Caliper DNA Analysis Plate
Technology Analysis: Analysis Systems
Caliper DNA Chip
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Drug discovery
Microarrays, microfluidic systems
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Drug development: “High Throughput Screening”
New drugs to the market faster
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Microtitre plates
Microreactors
“Pharmakogenomics”
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Study the genes role in metabolizing drugs
Individual and different reactions on patients
Select the right type and dose for new drugs
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Benefits of Biomicrotechnology devices
In Vivo: MEMS technology is significant for the future
development of medical implants and devices
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More functionality
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Biocompatibility
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Combination of microstructures and bioactive molecules
Suitable packaging, biocompatible coatings
Silicon can be made biocompatible and even biodegradable!!
Cost
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Batch manufacturing
Disposable analyzers and sensors
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Benefits
In Vitro Devices
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Biomolecular and biochemical analysis
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Miniaturization
Parallelization
Acceleration
Speed up drug discovery
Powerful new diagnostic tools
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Genetic analysis for the daily medical routine
Decentralized monitoring
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