2004

Microsystems in Biomedical EngineeringMicrosystems in Biomedical Engineering

byOddvar Søråsen

Department of Informatics, UiO23. March, 2004

2004

Microsystems in Biomedical EngineeringMicrosystems in Biomedical Engineering

Material from course by FSRM“Swiss Foundation for Research in Microtechnology”EPFL, Lausanne, 10 - 11 March, 2004

Focus: Miniaturization of devices useful in biomedical engineering

Micromachining and MEMS technologiesare powerful tools!

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ContentsContents

Definitions

Technology and principles

Applications

Benefits

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TermsTerms

MEMS (Microelectromechanical systems)Miniaturization of electrical, mechanical, optical, fluidic, magnetic systems

Microtechnology (e.g. MRL)Microsystems (Europe), MSTMicromachines (Asia)“Biomicrotechnology”

Wide and highly dynamic field Many different technologies Typical: biomolecules/cells will be combined with technical structures

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““BiomedicalBiomedical”” applicationsapplications

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 andmicrofluidic systems will grow tremendously!

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TechnologyTechnology

Microfabrication: batch processing from IC -> expandedPhotolithographyBulk micromachiningSurface micromachining (sacrificial + structural layers)

Silicon, a central material:+ mechanical properties (stress – strain, “spenning – tøyning”), + excellent piezoresistive material- optical penetration

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Non-silicon microfabrication

Metal (electroplating) Used directly or as mould (plastic) (Ni, Cu, Au)

Laser (cutting, removing glass, plastics, ceramics)Glass microstructuresPlastic microstructures (laminate)Hybrid microstructures

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Hewlett Packard Inkjet Nozzle Roadmap

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MEMS structures and principles

Pressure sensors bending of beams, diaphragm

Inertial sensors (accelerometers and gyros)

Detection mechanisms: piezoresistive elements, capacitive detection

Fluidic systemsActuators (mirror deflection)

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Applications in Biomedical EngineeringApplications in Biomedical Engineering

In Vivo systems (contact with patient bodies)A. Electrical stimulationB. BiosensorsC. MIS Minimally invasive surgery

In Vitro systems (clinical settings)Medical diagnosticsR&D in drug discovery and development

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A. In Vivo: electrical stimulationA. In Vivo: electrical stimulation

Neurostimulators in the cardiovascular areaPacemaker, 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) Commercialized Widespread use in children with profound deafness.

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A. In Vivo: electrical stimulation, A. In Vivo: electrical stimulation, contcont..

Retinal implants (futuristic) (Ophthalmology)Visual systems to the blindEpiretinal implant device: Optobionics

FES functional electrical stimulation 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 rehabilitationNeurology and rehabilitation

Limb function restorationSensors for prosthetic devicesFreehand system from NeuroControl Corp

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

TelemetryRF MEMS, inductive coupling

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NeuralNeural--electronic interfaceselectronic interfaces

Micromachined neural sensors and stimulators control prosthetic limbs with signals from the brain or spinal columnMEMS:

many electrodes co-fabricatedtailor systems to the dimensions of individual cells

Blocking brain signals that cause tremor (Parkinson) Medtronic

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Drug deliveryDrug delivery

AeorosolAsthma, attack prevention

Implantable drug infusion pumps (1980- to cancer pat.)Small pump controlled by an electronic module Biotelemetry unit, lithium batteryRefillable 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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Technology Analysis: Drug Delivery

Nebulisers for drug inhalers

STEAG microParts, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG

Boehringer Ingelheim (D)STEAG microParts (D)

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Technology Analysis: Drug DeliveryDebiotech Chip

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Technology Analysis: Drug Delivery

Source: Debiotech

Debiotech Chip

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Patches, Patches, stentsstents

Transdermal patch systems For transcutaneous delivery of drugs (“passing, entering, or by penetration through the skin”)Electrophoresis are usedAt an advanced clinical trial stage

Stents!

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B. In Vivo: B. In Vivo: biosensorsbiosensors

Sensors typically measure physical rather than biochemical parametersPressure sensors inserted into a catheter and inserted into arteries (blood, bladder, cerebral spinal pressure)

Blood pressure sensors used during surgerymeasuring intravascular blood pressure

Brain pressureHighly invasive brain surgeryPatient 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.

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Technology Analysis: Monitoring & P.O.C

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B. B. BiosensorsBiosensors, , contcont..

Catheters (RADI) and endoscopes

Ultrasound blood pressure

Gasteroentology: Swallowable cameraImaging Ltd, IsraelCMOS image sensors, ASIC, LED illumination, video telemetry, UHF radiotelemetry up to 5 hours (small intestine)

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Technology Analysis: Catheters & EndoscopesGiven Imaging – Imaging System in a Pill

Wireless linkWired link

Source; Given Imaging Ltd

Optical lensand CMOSimager

Battery Radio transmitter

Pill - 11mm diameter 27mm long

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B. B. BiosensorsBiosensors, , contcont..

DiabetesLarge activity Commercial product:

GlucoWatch from Cygnus, CGMS sensor systemSpectroscopy used

No in vivo sensors in common use for monitoringmetabolics

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.

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C. MIS Minimally Invasive SurgeryC. MIS Minimally Invasive Surgery

“Keyhole surgery”MicromanipulatorsMiniaturized surgical microinstruments

Toolbox:Micropump, microvalves, microfilters, microneedles,microsyringes (sprøyter), incredibly sharp blades

Pressure monitors are usedCatheters with imaging capabilities, incl. ultrasonic probes

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In In VitroVitro devices: devices: BiochipsBiochips

Miniaturize entire biomedical systems

Microfluidic systems typically haveSmaller volume, reduction of system sizePrecise control of sample volume

thermal, fluidicMassively parallel testsPossible reduction in system cost

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In Vitro: Main technologiesIn Vitro: Main technologies

Lab-on-chip devicesIntegrate different biochemical laboratory processes on a single chip

Microarrays

Application areas:Monitoring: blood pressure, glucose, blood gas ++Life science research and drug discovery

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Technology Analysis:Glass Microreactors

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LabLab--onon--chipchip

Blood analysis at the bedside (“point-of-care” testing) Systems are microfluidic basedTiny channels etched in the chip, glass, plasticTransport of droplets of fluid by electrophoresesTiny pumps and valves in some cases

- most without moving partsCD (centrifugal force), SAW

Single use chip (HP and iSTAT), 2 min, 2-3 drops

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iSTAT

• blood analysisglucose, urea, pH, blood gases,

• portable POC device• analyser + disposable cartridges• microfluidic channels• micro-fabricated thin-film electrodes

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iSTAT Sensor Chips

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MicroarraysMicroarrays

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 analysisMicrosystems for genetic analysis

Gene chips DNA analysis Calipher DNA analysis plateFragment of genome is identified on a chip surface

DNA amplification

Protein chipsDifferent proteines or peptides are identified

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Glass Microstructures Example

Caliper DNA Analysis Plate

Caliper DNA Analysis Plate

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Technology Analysis: Analysis Systems

Caliper DNA Chip

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Drug discoveryDrug discovery

Microarrays, microfluidic systemsDrug development: “High Throughput Screening”New drugs to the market faster

Microtitre platesMicroreactors

“Pharmakogenomics”Study the genes role in metabolizing drugsIndividual and different reactions on patientsSelect the right type and dose for new drugs

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Benefits of Benefits of Biomicrotechnology Biomicrotechnology devicesdevices

In Vivo: MEMS technology is significant for the future development of medical implants and devices

More functionalityCombination of microstructures and bioactive molecules

BiocompatibilitySuitable packaging, biocompatible coatingsSilicon can be made biocompatible and even biodegradable!!

CostBatch manufacturingDisposable analyzers and sensors

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BenefitsBenefits

In Vitro DevicesBiomolecular and biochemical analysis

MiniaturizationParallelizationAccelerationSpeed up drug discovery

Powerful new diagnostic tools Genetic analysis for the daily medical routineDecentralized monitoring

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