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© 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 3
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 4
Necklaces/patches Watch-type Headsets Base Stations
© IMEC 2010
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 5
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
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 6
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
acceleration models?
Failure: - safe failure mode
- change device if failure
Cheap disposable device
typical requirements: FLEX
Embedding*
* Wafer and board level technologies (trade off between cost and density)
© IMEC 2010
UTCP: ultra thin chip package
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 7
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 8
• 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 9
© IMEC 2010
Current focus of UTCP: process optimization towards high reliability and process throughput
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 10
• 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 11
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
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 12
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
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
SMI: stretchable mould interconnect
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 13
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 14
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 15
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 16
‘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
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 17
FLEX
Embedding*
STRETCH carriers*
* Wafer and board level technologies (trade off between cost and density)
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
Failure: - safe failure mode
- change device if failure
Cheap disposable device
typical requirements:
© IMEC 2010
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 18
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
Failure: - safe failure mode
- change device if failure
Cheap disposable device
typical requirements:
In the body:
??
© IMEC 2010
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 19
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
Failure: - safe failure mode
- change device if failure
Cheap disposable device
In the body:
Wearing comfort, minimum FBR: • miniaturization
• biocompatibility ( ~application)
• biomimetic package
Reliability: extremely good• mechanical properties
• storage environment
• hermeticity
• sterilization
life time: weeks ... ~70 years
Testing: - duration??
- uncertainty of bio-testing
- strongly dependent on application
Failure: - safe failure mode
- failure is often not immediately
known extreme reliability Cost can be higher
(operation cost, insurance)
typical requirements:
© IMEC 2010
Packaging for wearable medical applications
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 20
On the body:
Wearing comfort important
small, thin
flex, stretch
Reliability: very good• mechanical properties
• storage environment
life time: days ... weeks
testing: duration is long but feasible
Failure: - safe failure mode
- change device if failure
Cheap disposable device
In the body:
Wearing comfort, minimum FBR: • miniaturization
• biocompatibility ( ~application)
• biomimetic package
Reliability: extremely good• mechanical properties
• storage environment
• hermeticity
• sterilization
life time: weeks ... ~70 years
Testing: - duration??
- uncertainty of bio-testing
- strongly dependent on application
Failure: - safe failure mode
- failure is often not immediately
known extreme reliability Cost can be higher
(operation cost, insurance)
typical requirements:
© IMEC 2010
Biocompatibility of materials
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 21
• 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 22
• = 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!
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 23
• 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 24
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 26
• 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
MAAIKE OP DE BEECK – ESTC – BERLIN, SEPT 2010 27
• 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 28
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
- all materials are ‘biocompatible’
- 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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 29
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
- all materials are ‘biocompatible’
- 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)
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 30
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 31
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 32
• = 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:
MAAIKE OP DE BEECK – ESTC – BERLIN, SEPT 2010 33
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 34
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 35
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 36
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 38
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 39
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
* Wafer and board level technologies (trade off between cost and density)
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
MAAIKE OP DE BEECK – INEMI WORKSHOP – BERLIN, SEPT 2010 40
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