Implantable

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Implantable MEMS

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Outline

Sensors for biomedical applications (Bio-sensors)– Application of pressure sensors

StentsImmuno-isolation devicesDrug delivery systems

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Introduction

Micromachined pressure sensors are one of the most

commercially successful MEMS applications

Possibly oldest MEMS application: more then 30 years ago

Piezoresistive phenomenon reported in 1961,

mass production of pressure sensors since 1974

Applications: automotive, aerospace, biomedical, industrial

Types: piezoresistive, capacitive, piezoceramics

Market of 1bn in 2001, will continue increase

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Why MEMS pressure sensors

Small size, mass production, integrated electronics (transducer/transmitter)Silicon- excellent mechanical proprieties that recommend it for mechanical sensors:– Linear elastic (plastic modification only after heating at

600OC)– Low hysteresis– Chemically inert– Strong piezoelectric effect

Device fabrication and packaging using similar microelectronics technology (standard process)Low cost (chip ~ 0.1-0.3 USD, sensor ~ 2-5 USD)

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Types of pressure sensorsPiezoresistive pressure sensorCapacitive pressure sensorsOptical pressure sensorsPiezoceramicAFTER REFERENCE PRESSURE:

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Basic concept- piezoresistive pressure sensor

A thin diaphragm generated in the bulk siliconEmbedded piezoresistors on diaphragm to measure strainBridge circuit + amplifying and tuning electronics for signal processing/conditioningPackaged according to application requirements

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Piezoresistive transductionApplied stress/strain affects resistance in piezoresistive materialsDiscovered in Si in 1954 (Bell labs)Physics: majority carrier mobility affected by stress:

– In p-type Si, hole mobility decreases: R increases– In n-type Si, electron mobility increases: R decreases

Advantages:– Simple fabrication– Simple interface circuits: measure change in R using a simple

Wheatstone bridge topologyDisadvantages:

– Temperature sensitive– High thermal noise

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Piezoresistive transduction

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Piezoresistivity in single crystal Si

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Piezoresistive Sensor Interfacing

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Layout of pressure sensors

Pressure sensors layout

Optical image of pressure sensor

pressure sensor wafer

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Anistropically etched cavity

Masked region- <100> plane

<100> plane

<111> planes

SEM picture with pressure sensors diaphragms

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Generic process flow for pressure sensor

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Generic process flow for pressure sensor

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Application:Catheter pressure sensor

Henry Allen, Kamrul Ramzan, Jim Knutti, and Stan Withers

A Novel Ultra-miniature catheter tip pressure sensor

fabricated using silicon and glass thinning techniques

MRS Conference, San Francisco, CA 2001

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Catheter pressure sensor

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Catheter pressure sensor

Top-side Sensor process

Bonding and thinning sequence

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Capacitive pressure sensorsHigh temperature operation (>125 degrees C) Low power consumption High overpressure capability and high resistance to pressure shocks Low temperature coefficient Ease of packaging

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Implantable microsystem for blood pressure measurements

Ziaie and Najafi

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Catheter pressure sensor (2)

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Fiber-optic pressure sensors

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Stents

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Stents

Stents are one method by which the size of arteries can be increased in patient with heart diseaseStents are also use to repair aneurismAre mainly fabricated from stainless steelTo improve the bio-compatibility: covering with TiN(sputtering)New trends: drug-eluting stents– Coating the stents with the pure drug– Drug + polymer solution applied on the stents surface– Wrapping the stent with a polymer sheath in which drug is embeded– Coating the stent with a photo-polymerizable gel in which drug is

immobilized– Fabrication of drug-containing reservoir into the struts of the stent

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Stents coated with photogel for drug delivery

Y. Nakayama, et alDevelopment of high-performance stent: Gelatinous photogel-coated stent that permits drug delivery and gene transferJournal of Biomedical Materials ResearchVol. 57, Issue 4, 2001,

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Stents with Drug Containing Reservoir Material:- Cobalt – chromium - Stainless steel

www.conormed.com

Stents fabricated by Conor Medisystem

- The drug and polymer are protected in hundreds of deep, non-deforming reservoirs.-The reservoirs provide up to 6 times the drug dose capacity compared to surface-coated stents.- There is far less polymer contact with the vessel wall than with a surface-coated stent, so the inflammatory tendencies of drug delivery stenting is reduced.

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Immunoisolation devices

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Immunoisolation devicesState of the art: semi-permeable polymer based capsule (e.g. to isolate implanted islet cells from surrounding biological environment)Polymer based capsules (disadvantages):

• Inadequate mechanical strength• Broad pore size distribution

These factors can cause mechanical failure of the capsule and immunorejection due to the diffusion of antibodiesSolution: microfabricated silicon capsules (nano-porous silicon membrane)Advantages:

• Reproducibility of small features• Greater mechanical strength

Requirements:• Stability• Non-biodegradability• Biocompatibility

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Immunoisolation devices

Tejal A. Desai et al Microfabricated Biocapsules Provide Short-Term Immunoisolation of Insulinoma XenograftsVolume 1, Issue 2, Jan 1999 , Pages: 131-138, Biomedical Microdevices

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Immunoisolation devices- Fabrication Process

The main steps of the fabrication process:

a) Trench fabrication (deep RIE)

b) SiO2 deposition (PECVD, LTO)

c) Patterning of oxide, PolySi deposition, patterning PolySi

d) Wet etching of SiO2 (exposed area)

e) Bonding (silicon elastomer)

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Immunoisolation devices- Fabrication Process 2

SEM of fabricated membranes

Fabrications steps: a) polySi deposited on Si3N4 layer b) etching holes in PolySi layer c) SiO2 growing d) patterning of anchor points and depositio of polySIplug layer e) planarization, f) deposition of protective SI3N4 layer g) membrane etching, removing Si3N4 and etching SiO2 in HF

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Drug delivery

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Drug Delivery Systems

Advantages of implantable systems:

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Silicon Microreservoir Devices for Drug Delivery

Santinni et al, MicroChips

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Fabrication process

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Device Filling Process

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Theory of Operation

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Drug Released Mechanism

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Bio-adhesive Microdevices for Drug Delivery

Fabrication processa)SiO2 (thermal oxide)b) PolySi- LPCVDc)) LTO- PCVD d) photolithography e) RIEf) photolithographyg)KOH etching

Drug attach to the SiO2 chip!

A. Ahmed et al “BioadhesiveMicrodevices for Drug delivery”Biomed Microdev. 2001

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Polymer Microreservoir DevicesDiscontinuous dewetting can fill large arrays of microwells.(A)Schematic illustration of an array of microreactors filling with liquid.

(B) Optical micrograph of wells (10 ím diameter; 2.2 ímdeep) in a PDMS surface filling with tri(ethylene glycol).

(C) Optical fluorescence micrograph of a microtomedsection through wells filled with epoxy (Epo-tek UVO114) containing Rhodamine B.

(D) Empty wells (right) and wells filled with a solution of brilliant green in tri(ethylene glycol) (left) by discontinuous dewetting.

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Smart Drug Delivery (Smart pills!)Marc Mandou

http://mmadou.eng.uci.edu/

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Smart Drug Delivery (Smart pills!)

Documents

Implantable