Wearable and implantable packaging for biomedical devicesthor.inemi.org/webdownload/newsroom/Presentations/Med_Pkg_Sept20… · Wearable and implantable packaging for biomedical devices

© IMEC 2010

Wearable and implantable packaging

for biomedical devices

Maaike Op de Beeck

Imec, Leuven, Belgium

iNEMI workshop Sept. 2010

© IMEC 2010

Introduction

IMEC: Research institute since 1984

Initially: research mainly focussed on CMOS scaling “law of Moore”

Later: growing attention for Advanced Packaging, for MEMS , ...

Recently: strongly growing interest for various other research topics.

“More than Moore” activities, such as Research for medical

applications (wellness and health)

• Adjusted circuit design for wearable health monitoring systems (dedicated

biopotential read-out for EEG & ECG, ULP circuits, wireless communication...)

• System design for wearable health monitoring systems

• power management and energy scavenging for wearable systems

• devices for in-vitro and in-vivo analysis of neuron activity

• Bio-sensors

• Devices for in-vitro diagnostics, microfluidics, Lab-on-Chip

• Packaging for medical applications: - Wearable devices

- Implantable devices

MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 2

© IMEC 2010

Wearable systems for health and wellness improvement : examples


Ambulatory EEG (Electro-Encephalogram) in 1cm3

decrease of power consumptionand dimensions

Added

power layer

(voltage regulator)

with compact 150mAh

Li-ion battery

60 hours energy autonomy

(8 channels, 512Hz)

© IMEC 2010

Wearable systems for health and wellness improvement : examples


Necklaces/patches Watch-type Headsets Base Stations

© IMEC 2010

Packaging for wearable medical applications


On the body:

Wearing comfort important

small, thin

flex, stretch

Reliability: very good• mechanical properties

• storage environment

life time: days ... weeks ... months

testing: duration is long but feasible

acceleration models?

Failure: - safe failure mode

- change device if failure

Cheap disposable device

typical requirements: FLEX

Embedding*

STRETCH carriers*

* Wafer and board level technologies (trade off between cost and density)

© IMEC 2010



On the body:


small, thin

flex, stretch



life time: days ... weeks


acceleration models?





Embedding*


© IMEC 2010

UTCP: ultra thin chip package


Highly flexible package

Chemically inert

Si chip: ~20µm thick

Total UTCP: ~60µm thick

PI: chemically inert

© IMEC 2010

Embedding of UTCP into std. multilayer flex board


• Thin package laminated in adhesive layer between two (large) flex panels

• Chip contacting through standard via drilling & metallization process

• Only minor modifications to flex PCB processing line needed

UTCP provides 2 fan-outs :

(1) Easy testing before integration

(2) Compatible with std. flex substr.

(2)

(1)

© IMEC 2010

UTCP integration example: ECG demonstrator


© IMEC 2010

Current focus of UTCP: process optimization towards high reliability and process throughput


• Environmental tests :using imec‘s dedicated interconnect test chip• Hot/humidity storage at 85% rel. humidity & 85°C, up to 1000h

• thermal cycling : -40/+125°C, up to 1000 cycles

Many tests are still ongoing or scheduled for near future.

• Functionality during and after static mechanical load /bending

– Tests are ongoing. First test results are available.

– Very promising results, only for strong bending (R<10mm) some temporally artifacts have been observed on very few UTCP’s.

• Functionality during and after dynamic mechanical load

Testing of mechanical and electrical properties of UTCP after very long testing period

R

Experimental setup for bending of UTCP embedded die, with cylinders having diameters of 5, 10, 15,…, 40 mm

time to electrical measurement

setupUTCPcompressible substrate

Moving cylinder

© IMEC 2010

Possible applications for thin flexible die package


Multi-die package:

complete integrated flexible system

extreme miniaturizationesp. in case of high density

interconnects

flexible embedding (polymer)

metallization

thin die

Single die package:

as ‘flexible interposer’

in a larger flexible

or stretchable device

Single die package:

as ‘flexible package’

between commercial flex

PCB, in a larger flexible

device

Wafer and board level

technologies

(trade off between

cost and density)

© IMEC 2010



On the body:


small, thin

flex, stretch









Embedding*

STRETCH carriers*


© IMEC 2010

SMI: stretchable mould interconnect


Stretchable

matrix

• Fabrication of stretchable wiring to connect

• Individual components

• rigid/flexible component islands

• stretchable wiring meander-shaped interconnects

Molding of device in silicone:to provide stretchable matrix for

- good mechanical support

- corrosion resistance

Functional

‘non-stretchable’

island

Fabrication of non-stretchable islands using:

• conventionally packaged electronic

components

• UTCP embedded in flex

© IMEC 2010

Examples SMI technology


Fitness monitor (with third party) Baby monitor (with third party)

Respiration sensor connections

Buzzer connections

Lesson learned: attention for transition stretch/flex/rigid for optimum reliability

© IMEC 2010

Reliability characterization :

detailed analysis of failure mechanisms


Design improvements based on simulation and experiments

- horse shoe shape

- multi-line design

Predicted failure locations after stretching

Shear strain induced local distortion

Failure mode

EXAMPLE: In-plane shear strain contour mapping @ 30% strain

(In-situ stretching SEM micrograph vs. FEM modeling)

Before stretching

After a few

stretch cycles

After many

stretch cycles

© IMEC 2010

Current focus of SMI: process optimization towards high reliability and process throughput


‘Old’ samples 5 improved samples

Process optimization:

• supported component

islands

• optimized PDMS shape

time

older

technoimproved techno

Strongly improved lifetime!

Reliability test :

cyclic strain of 10%

@ 1%/s strain rate

© IMEC 2010



FLEX

Embedding*

STRETCH carriers*


On the body:


small, thin

flex, stretch








typical requirements:

© IMEC 2010



On the body:


small, thin

flex, stretch









In the body:

??

© IMEC 2010



On the body:


small, thin

flex, stretch








In the body:

Wearing comfort, minimum FBR: • miniaturization

• biocompatibility ( ~application)

• biomimetic package

Reliability: extremely good• mechanical properties


• hermeticity

• sterilization

life time: weeks ... ~70 years

Testing: - duration??

- uncertainty of bio-testing

- strongly dependent on application


- failure is often not immediately

known extreme reliability Cost can be higher

(operation cost, insurance)


© IMEC 2010



On the body:


small, thin

flex, stretch








In the body:

Wearing comfort, minimum FBR: • miniaturization

• biocompatibility ( ~application)

• biomimetic package

Reliability: extremely good• mechanical properties


• hermeticity

• sterilization

life time: weeks ... ~70 years

Testing: - duration??

- uncertainty of bio-testing

- strongly dependent on application


- failure is often not immediately

known extreme reliability Cost can be higher

(operation cost, insurance)


© IMEC 2010

Biocompatibility of materials


• Biocompatibility: the ability of a material/device to perform with an appropriate host

response in a specific application (Ratner, 2004)

In practical words: a biomaterial

- does not evoke a toxic, allergic or immunologic reaction

- does not harm or destroy enzymes, cells or tissue

- does not cause thrombosis or tumors .... etc

• This is function of:

– the place in the body : - tissue

- bone

- blood

– the duration of the contact / exposure: - limited (<24 h)

- prolonged (24 h – 30 days)

- permanent (> 30 days)

– type of device contact: - surface (electrodes, transdermal delivery devices,..)

- external communication (urinary catheters, endoscopes,..)

- Implants: tissue and bone / blood (bone screws, sutures /

vascular stents,..)

• biocompatibility is contextual, i.e. much more than just the material itself will

determine the clinical outcome of the medical device of which the biomaterial is a part.

© IMEC 2010

Test tableISO10993


• = ISO Evaluation tests for

consideration

F = additional tests which

may be required for US

submissions

1: tissue includes tissue fluids

and subcutaneous spaces

2: for all devices used in

extracorporeal circuits

3: depends on specific nature of

the device and its component

materials

ISO10993:

is only a guideline

it remains difficult to

determine best testing

procedure

© IMEC 2010

Tissue response to biomaterial ... and vice versa!


• biocompatibility:

important for in-vitro devices containing living cells or tissue

much more stringent requirements for implantable devices:

No interaction with single cells but with living organism

Organism has series of mechanisms to react towards

implanted material (foreign body reaction)

Many pathways exist in organism to obtain finally same result

• Also tissue and body fluids will

influence the biomaterial/device.

examples:

– leaching of body fluids into implant

– diffusion of products into the implant

– chemical degradation i.e. oxidation (super-oxides during FBR!)

– response to mechanical stress (i.e. wear, fatigue)

tissue

biomaterial

© IMEC 2010

Foreign Body Response: tissue response of organism on implantation of a biocompatible material

Picture: Castner, D.G. and B.D. Ratner, Biomedical surface science: Foundations to frontiers. Surface Science, 2002, p. 28-60


Implantation Protein adsorption acute inflammation: neutrophils & macrophages

try to digest the implant

macrophages secrete protein signaling agents and form

foreign body giant cells producing superoxides

start of fibrous encapsulation & neovascularization

Final situation: thick fibrous tissue is covering implant

© IMEC 2010

Foreign body reaction

MAAIKE OP DE BEECK – ESTC – BERLIN, SEPT 2010 25

Aspirated vegetable material in lung, engulfed by macrophages and

FB giant cells, and surrounded by a fibrous encapsulation,

as protective shell for the lung tissue. Picture: www. granuloma.homestead.com

Each healthy human body tries to get rid of foreign material:

1. white blood cells, macrophages and FB giant cells try to engulf the material and digest

it by secreting superoxides.

2. finally a fibrous encapsulation is formed to insulate the foreign material.

© IMEC 2010

Consequences of foreign body reaction


• Weather the FBR is problematic or not, depends on the design and intended use of the implant.

• FB encapsulation isolates implant from host problematic for devices designed to interact with body device failure

– glucose sensors: sensitivity drops

– Pressure sensors: decrease of motility of membrane

– Electrodes: impedance increases

– Implanted drug delivery devices: apertures for drug release get clogged

• FB encapsulation might cause chronic pain due to chronic inflammation , i.e. when implants loose small particles by friction, by degradation

i.e. hip implant: after 10 years of successful operation, the surface starts to erode due to continuous friction. All eroded particles will migrate to the surrounding tissue, and each particle will be encapsulated -> chronic pain

© IMEC 2010

Intro: conventional biomedical packaging


• Typical packaging for medical electronic implant: Ti box– well known, biocompatible -> safe, NDA-approved

– big/huge box compared to ‘active’ content of packaging

– pronounced ‘foreign body reaction’ (FBR), risk on biofilm formation

• Example: pacemaker:

• Disadvantage of large size / rigid ‘foreign’ material:– Large implant: larger incision, more invasive for patient (short/long term)

more risk of infection, biofilm formation…

– Risk of irritation and chronic infection due to mechanical friction

– FBR often results in malfunctioning of sensors or electrodes

More advanced package? Requirements?

© IMEC 2010

Imec’s biocompatible packaging proposal


Phase 1:

wafer level chip package

Feedthroughs Top cover layer(s)

Bottom cover layer(s)Outer encapsulation

CMOS, MEMS,..

Main function:

- Die encapsulation by diffusion barrier

- Creation of feedthroughs

- all materials are ‘biocompatible’

Main function:

- mechanical support of total system

- electrical connections between dies

- creation of functional feedthroughs


- flexible package to reduce body reaction after implantation

Phase 2: (sub-)system package /

interposer:

biocompatible interconnect and

embedding of various dies

die 1 die 2

© IMEC 2010

Introduction


Phase 3: system package:

global biocompatible interconnect and

embedding of various dies, battery,...

Main function:

- mechanical support of total system

- electrical connections between dies

- creation of functional feedthroughs


- If possible: biomimetic package(flexible, texture)

die 1 die 2 battery

All electronic parts are embedded first, to form a subsystem assembled

on a flexible interposer

Second flexible global embedding

Metallization to connect electronic sub-part with

other sub-partsGlobal

feedthrough

© IMEC 2010

Phase 1: encapsulation of individual dieswafer level based process (2)


SEM showing the sloped silicon edges of thinned dies (~70um thick chips): the slope on both sides of the Si dies is made by sloped dicing using a dedicated

dicing blade.

Note that the dies are seen from the backside, at the top the dies are covered with a 1.5um thick capping layer (bottom side in the picture!).

Phase 1:

wafer level chip package

Feedthroughs Top cover layer(s)

Bottom cover layer(s)Outer encapsulation

CMOS, MEMS,..

© IMEC 2010

Validation: oxide step coverage


1

SEM pictures showing the excellent step coverage of a ~1.5um thick oxide used as top capping layer.

A dedicated low temperature oxide deposition process at 350°C is used.

3

oxide

copper

nitrideoxide

silicon

1.65µm

2

nitrideoxide

silicon

oxide

1.4µm

1.56µm

Thinned Si chip

2

1

3

© IMEC 2010

Test tableISO10993


• = ISO Evaluation tests for

consideration

F = additional tests which

may be required for US

submissions

1: tissue includes tissue fluids

and subcutaneous spaces

2: for all devices used in

extracorporeal circuits

3: depends on specific nature of

the device and its component

materials

ISO10993: document

describing

biocompatibility tests

is only a guideline

it remains difficult to

determine best testing

procedure

Type of test

Type a

nd d

ura

tion o

f conta

ct

cytotoxicity

© IMEC 2010

3 test samples for our diffusion characterization:


Si substrate

Oxide capping layer

(2 x 0.8um low temperature oxide)

PDMS

Cu-layer: back-end Cu patterns,

std. damascene process,

250nm thick Cu, ~60% Cu density

Petri dish

Std. passivation layer

Std. passivation layer

(50nm SiC, 400nm SiO2, 500nm Si3N4)

Cu-layer, damascene

Only Cu - control

Passivation

Passivation+ oxide Cu-layer, damascene

© IMEC 2010

Validation: in vitro co-culture – 3T3 fibroblast


co-culture with 3T3 fibroblasts (cell line) and 1 single test die After 1 week : morphology test

Control:

3T3

medium

copper

passivation

passivation + oxide

copper passivation passivation + oxide

Control: cells in good

condition

Almost no cells alive,cells in bad condition

Most cells in good condition: Cu diffusion reduced good test procedure ?

3T3 cell line = strong cells!

© IMEC 2010

Validation: in vitro co-culture - cardiomyocytes


co-culture with neonatal cardiomyocytes (primary cells)

After 5 days: live/dead cell assay with Calcein-AM

copper

passivation

passivation + oxide

Fluorescent intensity

figure of merit for amount of cells being alive

Encapsulation is functioning very well as

diffusion barrier forimplants in heart tissue

© IMEC 2010

Work ongoing - phase 2: Interposer-like package


IMEC’s board level ultra thin chip package (UTCP)

• biocompatible interconnect and embedding of various dies

• might be board level (cheaper) or wafer level (higher pitch density)

• biocompatible materials required

for IMEC’s UTCP:

- PI selection depends on application (wearable or implantable device)

- metallization (now Cu) needs to be adjusted for long term implants

die 1 die 2

© IMEC 2010

Work ongoing - phase 3: global embedding

37

Only a very thin

silicone layer is

covering the pressure

sensor in order to

realize sufficient

hermeticity without

loosing the sensor

functionality.

battery

Electronics

on PCB

Pressure sensor

die 1 die 2 battery

silicone molding interconnect (SMI) technology using biomedical grade silicone

fabrication of an implantable

bladder pressure sensor:

Packaging and integration: IMEC: electronic system design: by KUL-MICAS, Belgium.

(SBO-Bioflex project)

• to embed all sub-devices

• typical board level process (cost)

• biocompatible materials required

IMEC’s SMI process

metallization (now Cu) needs to be adjusted for long term implants

future alternatives: biomimetic encapsulation? Drug containing encapsulation?

© IMEC 2010

IMEC’s biocompatible packaging proposal: Initial cost calculations for phase 1-2


Cost strongly related to production volume

suppose production of 100.000 wafers of 200mm diameter

• Encapsulation of individual dies *,

CR based fabrication : US $20-25 each wafer

• Interposer-like package *,

CR based fabrication: US $ 80 each wafer

• Platinum metallization

(sputtering, patterning by lift-off

or litho & etch): several 100 US$ per wafer

Dominant cost: Platinum metallization (mainly raw material cost)

Pt cost: problem for both wafer and board level technologies.

Essential: use of selective deposition technique (eg. electroplating)

* Cu based metallization

© IMEC 2010

Overview activities related to wearable and implantable packaging & integration


Hermetic and

biocompatible

packaging for

in- vivo appl.

Chip

THINNING

and thin

embedding*

FLEX

Embedding*

STRETCH carriers*

Supporting technologies:

Functional surfaces

Super-hydrophobic layersElectrodes on/in the body


Phase 1 Phase 2 - 3: Biocompatible sub-

device/system encapsulation

Sealing layers

Picture: www.scscoatings.com

Hermetic chip encapsulation3Dim.

out-of-plane integration

© IMEC 2010

Conclusions


Wearable and implantable packaging concepts are proposed

Integration and packaging for wearable devices: - IMEC’s UTCP and SMI technology small, flexible, stretchable

- currently: lot of attention for reliability and for process robustness

(throughput/yield)

Integration and packaging for implantable devices:

• Some general ideas – challenges are discussed

• Currently: a biocompatible packaging process is proposed

- Phase 1: encapsulation layers serve as diffusion barrier: testing?

- Phase 2-3: assembly of the sub-devices and global embedding using

wafer level processing (high pitch density) or board level

processing (cheaper)?

- In case of platinum metallization: cost effective deposition & patterning methods should be developed.

© IMEC 2010

Documents

Wearable and implantable packaging for biomedical devicesthor.inemi.org/webdownload/newsroom/Presentations/Med_Pkg_Sept20… · Wearable and implantable packaging for biomedical devices