Parylene-on-oil packaging for long-term implantablepressure sensors

Aubrey M. Shapero1 & Yang Liu1& Yu-Chong Tai1

Published online: 15 July 2016# Springer Science+Business Media New York 2016

Abstract This paper reports and analyzes the feasibility studyof a parylene-on-oil encapsulation packaging method of pres-sure sensors targeted for long-term implantation. Commercialbarometric digital-output pressure sensors are enclosed in sili-cone oil and then encapsulated in situ with parylene-C or –D(PA-C, PA-D) chemical vapor deposition. Experimentally, sen-sors encapsulated with 30,000 cSt silicone oil and 27μmPA-Dshow good performance for 6 weeks in 77 °C saline with>99 % of original sensitivity, corresponding to an extrapolatedlifetime of around 21 months in 37 °C saline. This work showsthat, with proper designs, such a packaging method can pre-serve the original pressure sensor sensitivity without offset,validated throughout accelerated lifetime tests. In experiments,wires on the prototypes are used for external electronics but itis found that they contributed to early failures, which would beabsent in real wireless versions, indicating a potential for evenlonger lifetimes. Finally, a verified model is presented to pre-dict the pressure sensor sensitivity of parylene-on-oil packag-ing with and without the presence of a bubble in the oil.

Keywords Packaging . Parylene . Implantable pressuresensor . Lifetime . Reliability . Long-term stability

1 Introduction

Continuous internal body fluid pressure monitoring, ratherthan snapshot measurements taken in the clinic, in organs such

as the heart, eye, brain, and bladder, is important to indicatehealth or progression of disease (Yu et al. 2014; Clausen andGlott 2014). Some examples of these diseases and symptomsto be monitored are restenosis, hypertension, heart failure,glaucoma, intracranial hypertension and urinary incontinence.Although telemetric techniques exist for some applications,none provides adequate precision and accuracy, and catheter-ization is very invasive and can increase risk of infection. Forexample, no piezoresistive pressure sensor has lasted morethan 1 month inside the body due to a variety of reasonsranging from electronics failure to sensitivity and offset drift.Note that both the sensitivity and offset drifts are the two mostcommon failure modes and are often caused by the accumu-lation of biological material on the surface of the device (i.e.,biofouling) which changes the mechanical properties of themembrane. Capacitive membrane-based implantable pressuresensors have had some success such as the FDA-approvedCardioMEMS® sensor, and preliminary clinical trials of anintraocular pressure sensor with recalibrations for continueduse up to 1 year. (Koutsonas et al. 2015; Yu et al. 2014).

This work then aims at packaging a commerciallyavailable pressure sensor device and maintaining its sen-sor accuracy for long-term application (e.g., >12 months)in the body. This work is a major extension of Shaperoet al. (2016). This packaging method is suitable for anysensor based on membrane def lec t ion , namelypiezoresistive or capacitive sensors. Piezoresistive sensorsare prioritized in this paper because commercialpiezoresistive pressure sensors are more popular in usedue to their greater linearity than capacitive pressure sen-sors, which can suffer from parasitic capacitances(Clausen and Glott 2014). Because the sensor’s siliconmembrane needs to be protected from the environment,the deflecting membrane is never in direct contact withbody fluids just like the circuitry of any medical implant.

* Aubrey M. Shaperoashapero@mems.caltech.edu

1 Electrical Engineering, California Institute of Technology, 1200 E.California Blvd, MC 136-93, Pasadena, CA 91125, USA

Biomed Microdevices (2016) 18: 66DOI 10.1007/s10544-016-0089-4

However, the deflecting membrane needs to mechanicallysense the environmental pressure.

The traditional way to protect pressure sensors is to use oilin a bulky, hermetic metal can, which attenuates power andtransmission signals (Wessel 1984; Yu et al. 2014; Jiang andZhou 2010). Previous work involving oil without metal totransduce pressure from an ideally compliant outer membraneto the sensor membrane injects the oil into a bag structure(Majerus et al. 2011; Cong et al. 2010). In contrast, this pack-aging technique encapsulates the entire sensor in oil beforecoating a layer of flexible parylene onto the oil. Parylene-on-oil chemical vapor deposition (CVD) has been investigatedfor making optical lenses out of oil (Gorham 1966; Kanet al. 2013; Nguyen et al. 2007) or to make isolated parylenefilms by separating the parylene after deposition (Keppner andBenkhaïra 2004; Binh-Khiem et al. 2011). In general, it ispossible to deposit parylene using CVD when the vapor pres-sure of the oil is low (<5 Pa) (Homsy et al. 2015). There is asmall stress in the film deposited, but it is weak enough to beignored for most purposes, such that the surface of the film isessentially the shape of the liquid surface (Binh-Khiem et al.2010). This approach using in situ parylene CVD coatinggreatly simplifies the sensor packaging encapsulation.

Most commercial pressure sensors have a layer of gel ontop of the membrane, which is sufficiently protective for use inair. Coating parylene directly on gel has been investigated forimplanted applications, but the gel absorbs gases, especiallywater vapor, and can swell (Yu et al. 2014). If the gel is di-rectly coated with parylene, the swelling of the gel can causesensitivity drift of up to 5 % (Wang et al. 2015). This workalso coated parylene directly on commercial sensors with gelwithout oil for comparison, and measurement drift and delam-ination problems were observed in saline soaking tests. Thus,gel is not a viable substitute for oil in pressure sensor packag-ing for long-term implantation.

Biofouling is a common failure mechanism and manyauthors have studied various ways, but with limited suc-cess, to reduce, minimize, and even prevent biofoulingthrough use of drug coatings, ultrasound, and even aera-tion and bubbles to dislodge biomaterial (Yu et al. 2014).A major feature of this packaging method is to toleratebiofouling on the outer parylene membrane so as to main-tain pressure sensing accuracy.

2 Design concept

For long-term implantation of a pressure sensor, the packagingmust protect the functionality of the circuitry and the accuracyof the reported pressure. Circuit functionality degrades due tocorrosion from water, water vapor, or ions exposed to thecircuit. Thus stopping or minimizing water or ions fromreaching the sensor is critical. Our approach is to change the

chemical environment that the sensor stays in, rather thansolely relying on a barrier. This is achieved by housing theelectronics in a hydrophobic liquid, such as silicone oil, toreduce the concentration limit of water vapor in the sensor’senvironment. In silicone oil, the saturation limit of water vaporis around 350 ppm at 37 °C (Liland et al. 2008). Here, siliconeoil is a better choice over cured silicone, because even thoughboth repel liquid water, only the silicone oil repels water va-por, while water vapor is drawn towards inevitable defects inthe silicone (Lutz et al. 2012). One purpose of the parylene isto encapsulate the oil in situwithout bubbles so the oil remainswhere it needs to be. The deleterious effect of bubbles onaccuracy is discussed later.

Next, sensor accuracy must be maintained. Factors thatdegrade accuracy include biological agents like cells, antibod-ies, or other biofouling agents that can attach to the sensingmembrane of a pressure sensor so as to change the flexuralrigidity of the membrane. Therefore, one needs a biocompat-ible and flexible membrane that can block both corrosivechemical agents and biological agents. For example, a com-posite parylene/platinum membrane could be used for en-hanced protection (Chang 2013). A membrane does enhanceresistance to agents and it also increases stiffness. With properdesign, however, we show in the following that simultaneousprotection and transduction of pressure is achievable. Theresulting concept is shown in Fig. 1.

3 Sensitivity model

A model to derive the relative sensitivity of a parylene-on-oil package, Sr, is presented here, where Fig. 2 diagrams thescenario. Ideally the sensitivity retention should be 100 %,i.e. Sr = 1.

In this model, other than the flexible membrane, the funnelwalls are rigid and the oil has a bulk modulus K. We assume a

Fig. 1 Concept for a packaged pressure sensor, covered bybiocompatible silicone oil, encapsulated by parylene. This packagingmethod addresses two failure modes, i.e., electrical corrosion anddevice drift. The electrical corrosion failure due to corrosion from ionsin the body is addressed by hydrophobicity of the silicone oil. Thesensitivity and offset drifts due to biofouling are addressed by the shapeand size of the parylene coating

66 Page 2 of 10 Biomed Microdevices (2016) 18: 66

fixed value of P0, the initial pressure inside the sensor cham-ber. The absolute sensitivity of a piezoresistive pressure sensoris reported in output voltage/supply voltage/unit pressure.Since the pressure sensor is submerged in oil, by definition,

Ssensor≡dVsensor=Vsupply

dPoilð1aÞ

And we can define the absolute sensitivity of the packagedsensor with respect to the environment of interest.

Spackage≡dVsensor=Vsupply

dPenvironmentð1bÞ

Thus, relative sensitivity after packaging is

Sr≡SpackageSsensor

¼ dPoil

dPenvironmentð2aÞ

because the relative voltage cancels out as the silicon mem-brane has not changed. We assume an initial conditionPenv. = Poil = P0, so we can rewrite (2a) as

Sr ¼ Poil−P0

Penvironment−P0ð2bÞ

Equations (3)-(6) are straight forward,

dPoil ¼ −K

VoildVoil ð3Þ

Voil ¼ V 1−V 2 þ V f unnel ð4Þ

dVoil ¼ V 1−V 2 ð5Þ

dPoil ¼ Poil−P0 ð6Þ

Substituting (4), (5), and (6) into (3) yields

Poil−P0 ¼ K

V 1−V 2 þ V f unnelV 2−V 1ð Þ ð7aÞ

In most cases Vfunnel ≫ V1 , V2, so we can simplify(7a) as such,

Poil−P0≈K

V f unnelV 2−V 1ð Þ ð7bÞ

Under the assumption of small deflections, the volumedisplaced by each membrane is linear with the pressure differ-ence across the membrane. We then define the volume-pressure compliance c as such,

V ¼ cp ð8Þ

Assuming a thick circular membrane, the deflection is(Schombur 2011),

w rð Þ ¼ pa4

64D1−

r2

a2

� �2

ð9aÞ

where flexural rigidity D ¼ Et3

12 1−ν2ð Þ, p is the differential pres-

sure across the membrane, a is the radius, E is Young’s mod-ulus, ν is the Poisson ratio, and t is thickness of the membrane.It can then be shown that,

V ¼Z a

02πrw rð Þdr ¼ pa6π

192D¼ cp ð10aÞ

for the volume-pressure compliance c, and the volume sweptis indeed linear with pressure for small deflections. Similarly,the derivation can be done for square membranes of sidelength 2a (Schombur 2011),

w x; yð Þ ¼ 2pa4

99D1−

x2

a2

� �2

1−y2

a2

� �2

ð9bÞ

and

V ¼Z a

−a

Z a

−aw x; yð Þdxdy≅ pa6

43:5D¼ cp ð10bÞ

Fig. 2 Funnel model representing a parylene-on-oil package to deriverelative sensitivity, Sr. The encapsulation is modeled with twomembranes. a The starting condition, where the environmental pressureand the oil pressure equal the sensor chamber pressure so that neithermembrane deflects. b The environmental pressure increases so as to causedeflections in both membranes

Biomed Microdevices (2016) 18: 66 Page 3 of 10 66

Applying (8) yields

V 1 ¼ c1 Poil−P0ð Þ; ð11aÞ

V 2 ¼ c2 Penvironment−Poilð Þ: ð11bÞ

Substituting (11a) and (11b) into (7b) results in

Poil−P0 ¼ K

V f unnelc2 Penv:−Poilð Þ−c1 Poil−P0ð Þð Þ ð12Þ

Combine like terms for the intermediate equation

c1 þ V f unnel

K

� �Poil−P0ð Þ ¼ c2 Penv:−Poilð Þ ð13Þ

One can get the relative sensitivity,

Sr ¼ Poil−P0

Penvironment−P0¼ c2

c1 þ c2 þ V f unnel

K

ð14aÞ

First of all, if the bulk modulus K is large, or the initialvolume of the oil (Vfunnel) is small, as are often the cases, thenwe can simplify (14a) to

Sr ¼ Poil−P0

Penvironment−P0¼ c2

c1 þ c2ð14bÞ

Thus, if c2 ≫ c1, then Sr ≈ 1, as desired. Since c∝ a6

t3 , increas-

ing the effective outer radius has a large impact on c2, makingit quite easy to achieve large enough volume-pressure compli-ance on the outer membrane such that loss of pressure trans-duction is negligible.

4 Fabrication and packaging method

To demonstrate and illustrate the packaging, miniature SPIdigital barometer (Freescale® MPL115A1) sensors are cho-sen because of the convenience of their built-in temperatureand linearity compensation. The sensors are dipped in incom-pressible 30,000 cSt silicone oil and then encapsulated bychemical vapor deposited (CVD) parylene. Parylene is usedas an isolation barrier from biomolecules to avoid direct bio-fouling of the sensor, while biofouling on outer parylene ismitigated and would not affect the pressure transmission dueto a large parylene surface area. This results in an oil packag-ing that is conformally sealed by parylene without bubbles inthe oil. By design, the oil droplet shape should have concavity,so even if the environmental temperature varies and causes oilvolume changes, the parylene will bend rather than expand.This is achieved by epoxying silicone posts to the package andusing high viscosity oil such that it could be hung upside-

down and not fall for a sufficiently long time that parylenecould be coated on the surface. Thus there will be no sensitiv-ity loss due to temperature effects. The packaging process fora Freescale® MPL115A1 pressure sensor is shown in Fig. 3.

A photograph of the final packaged device is shownin Fig. 4.

5 Experimental results

5.1 Sensor performance after packaging

Figure 5 shows that a typical packaged sensor drifts very littleover time. To separate stable offset induced by initial exposureto high temperature alone from offset drift caused by acceler-ated soaking in saline, the packaged sensor was thermally cy-cled between room temperature and 77 °C in air overnight.Calibration occurred after this thermal cycle, but before soakingin saline. Training set data was generated by recording thesensor’s 10-bit pressure and temperature outputs during pres-sure sweeps at 21 °C, 37 °C and 45 °C in air. After soaking in77 °C saline for two days, the packaged sensor was comparedto a control sensor in air at room temperature. The calibratedoutput has an error less than 1 mmHg, meeting the accuracyrequirement for most medical applications (Yu et al. 2014).

Fig. 3 Pressure sensor and wires are first soldered onto a PCB, and thensilicone posts are attached onto the sensor and PCB. Next, the sensor isdipped in hexane and then in 30,000 cSt silicone oil. Low-viscosity hex-ane works as a surfactant to fill the voids inside the pressure port,and then gets replaced by silicone oil later, which greatly accelerates thedegassing process. After degassing, the sensor is held face down in aparylene deposition chamber (top). The high-viscosity oil does not fallfor hours. A layer of CVD PA-C or PA-D is coated conformally on oil andon the rest of the apparatus (bottom)

66 Page 4 of 10 Biomed Microdevices (2016) 18: 66

The pressure sensor packaged with oil and parylene wasfound to have a quick pressure step response. A typical devicewith parylene-on-oil packaging is shown in Fig. 6.

5.2 Accelerated aging tests

Various pressure sensor packages were investigated for accel-erated soaking tests. A control sensor was uncoated and failedquickly as expected after 1 day in 67 °C saline. Some sensorswere coated with PA-C or PA-D without oil, but still retaininga layer of gel as produced by the manufacturer. The remainingsensors were packaged with 30,000 cSt silicone oil and en-capsulated with PA-C or PA-D. The results are summarized inTable 1. With the exception of the one with BOil +21 μm PA-C,^ all of the other devices were thermally baked in air over-night at the temperature which they were to be soaked toisolate sensitivity and offset drift due to elevated temperatureversus soaking time in saline. The relative sensitivity and off-set after thermal treatment, but before soaking in saline, are inthe BPre-Soak^ column.

One device was purposely not modified nor given a ther-mal regiment before soaking in 5000 cSt silicone oil at 97 °C,

since the water saturation limit increases at elevated tempera-tures. At 97 °C, the saturation limit of water is extrapolated tobe around 1000–1500 ppm (Liland et al. 2008). After the firstweek a small offset was induced, presumably due to thermaltreatment, but in the following weeks neither the sensitivitynor offset has changed. This confirms that silicone oil is notharmful to the pressure sensor. This sensor is expectedly stillfunctioning as of the writing time of this paper.

Roughly every 10 °C increase in temperature doubles thesoaking life-time acceleration factor according to the Arrheniusrelationship (Chang et al. 2013). It was found that thicker layersof PA-Cwould not survive higher temperatures in attempting toachieve faster acceleration factors so devices were insteadpackaged with PA-D due to its higher glass transition temper-ature so saline soaking tests at higher temperatures could morequickly and efficiently extrapolate lifetime at 37 °C.

Experimentally, the longest soaked device while maintain-ing adequate sensitivity and minimal offset is the one withBOil +27 μm PA-D,^ which lasted for 6 weeks at 77 °C,equivalent to 21 months at 37 °C. At this point a bubble wasobserved, due to the delamination of the parylene from thePCB, leading to a void volume during vacuum, which couldbe filled by air permeating through the membrane. However, aleak of oil was not observed.

The device with BOil +25 μm PA-D^ showed instability ingetting a signal in week 3 when it was noticed that the wiresused to connect the device to external electronics had falleninto the saline leading to corrosion. These wires would not bepresent in a final wireless device so they were not supposed tobe submerged in saline.

Recall that the sensors have a layer of gel on the membraneas delivered by the manufacturer. In all sensors, the gel has notbeen disturbed, so devices without oil still have a layer of gelbetween the silicon and parylene. Despite the presence of gel,two problems with direct deposition of parylene arise. First,

Fig. 4 Photograph of a finished sensor, which is made of a Freescale®MPL115A1 pressure sensor on PCBwith three silicone posts. The sensorinside is bathed in 30,000 cSt silicone oil, whose outer surface is latercoated with 27 μm PA-D

Fig. 5 Room temperaturecharacterization of a packagedsensor in 30,000 cSt silicone oil,coated with 27 μm PA-D. Anunmodified device has naturalstandard deviation of .0786 kPa,but otherwise assumed to readcorrect pressure. Due to thermalstress, an offset arises in thepackaged sensor, but the offset isstable and error is greatly reducedthrough calibration

Biomed Microdevices (2016) 18: 66 Page 5 of 10 66

even though the devices without oil but with B25 μm PA-D 1,2^ report output data up to week 4, 14 respectively, their off-sets drift much more than 1 mmHg (0.13 kPa), which is themaximum tolerance for most medical applications, after justone week. Second, devices without oil and with parylene likeB25 μm PA-D 1, 2^ exhibit smaller relative sensitivity becausemembranes stiffen as material accumulates on them, as ex-pected. Depositing 32 μm of PA-C in the deposition chamberdirectly onto two MPL115A1 pressure sensors gave them aninitial relative sensitivity of 0.913 ± 0.063. The true thicknessof parylene deposited on the sensor membrane is less than inthe deposition chamber due to a pinhole effect caused by thepressure port of the original housing. Thus this result under-estimates the severity of sensitivity degradation. For both rea-sons, parylene-on-oil packaging is superior to direct deposi-tion of parylene without oil.

6 Failure modes from soaking

6.1 Thermal stress

Silicone oil has a larger coefficient of thermal expansion(CTE) than parylene. At 25 °C, the volumetric CTE of PA-Dis 114 ppm/°C, and 940–1040 ppm/°C for oil (SCS ParyleneProperties 2007; Shin-Etsu Silicone 2004). Thus, if the devicehad a convex package, the parylene would be stressed at ele-vated temperatures. This is harmful at any elevated temperature,including the body temperature of 37 °C, but this effect is morepronounced during accelerated elevated-temperature aging tests.

Fig. 6 Pressure and temperature step response of a device with 30,000cSt silicone oil and coated with 27 μm PA-D. The pressure step responseof the packaged sensor is as fast as that of the unpackaged sensor. Notethat the temperature measurements are only for pressure calibration. Asexpected, the packaged pressure sensor experiences a different steadystate temperature in partial vacuum and a tempered temperature stepbecause the silicone oil has heat capacity. The strong correlation in thepressure step responses, which considers raw pressure and temperaturedata, indicates that the temperatures reported by both sensors are correct

Tab

le1

Accelerated

lifetim

esoakingtestofpackagingofvariousdevices.Thicknessofparylene

reported

isthatof

adepositedlayeronaglassslideinside

thedepositio

ncham

ber.Offsetisdefinedasthe

errorversus

controlatP

env.=75

kPa,roughlythecenter

oftheexam

ined

pressure

rangeof

1atm

to50

kPa

Package

Unit.Tim

e/Temp.

Pre-Soak

12

34

56

7

NoPackage

Day/6

7°C

S r1.015

Electronics

failu

reas

expected

with

noprotectionin

salin

eOffset(kP

a)1.753

Oil+25

μm

PA-D

Week/

77°C

S r0.996

1.000

1.001

0.999

Faileddueto

wirecorrosionon

week4

Offset(kP

a)−0

.854

−0.574

−0.204

0.061

Oil+21

μm

PA-C

Week/

87°C

S r1.050

1.026

1.073

1.023

0.996

0.248

Week5sensitivity

failu

reOffset(kP

a)0.423a

−19.4

−21.8

−21.3

−21.4

10.73

25μm

PA-D

1Week/

77°C

S r0.979

0.987

0.983

0.980

0.995

Delam

ination-inducedcorrosionsignal

failu

reatweek5

Offset(kP

a)48.37

52.47

53.12

48.52

55.50

5000

cStO

ilBath(nosalin

e)Week/

97°C

S r0.998

0.997

0.998

0.998

0.996

0.997

0.997

0.9969

Offset(kP

a)−0

.222

−0.468

−0.468

−.446

−0.410

−.443

−.420

−.433

25μm

PA-D

2Week/

77°C

S r0.971

0.974

0.978

0.955

0.972

0.969

0.986

0.976

Offset(kP

a)49.96

53.68

54.51

51.04

54.67

55.60

56.13

55.82

Oil+27

μm

PA-D

Week/

77°C

S r1.001

1.000

0.993

1.001

0.999

0.994

0.997

0.973

Offset(kP

a)−0

.512

−0.119

−0.048

0.300

−0.155

−0.02

0.286

1.116

89

1011

1213

1415

25μm

PA-D

2Week/

77°C

S r0.990

1.000

0.978

0.996

0.986

0.983

0.987

Corrosion-induced

erroron

week14,

failon

week15

Offset(kP

a)55.51

57.6

56.43

56.44

55.71

53.47

36.00

Oil+27

μm

PA-D

Week/

77°C

S rDelam

inationof

parylene

atwire/PC

Bjunctio

ncaused

bubbleatweek7.Electronics

wereintacton

week8

Offset(kP

a)

aThe

PA-C

packagewas

notthermally

stressed

before

soaking,

unlik

ethePA

-Dpackages.T

hus,an

offsetwas

createdduring

thefirstw

eekin

87°C

salin

e,whereas

theotherswerethermally

stressed

beforehand

66 Page 6 of 10 Biomed Microdevices (2016) 18: 66

Thus if a concave surface could be engineered, the parylenecoating would be able to bend, rather than expand, so as tocompensate thermal expansion. This desired concave surfacecould be achieved utilizing the oil surface tension and with posts,as shown in Fig. 7.

This idea was used to minimize possible microcracks dueto overstressed parylene during the accelerated soaking tests.The posts are seen in Fig. 3. Without posts, packages involv-ing thick parylene coatings would not survive even for shortperiods of time at elevated temperatures.

6.2 Presence of bubble in oil

Here, we expand the theory to include bubble effect to dem-onstrate the importance of a bubble-less encapsulation of oilby parylene. For a small minority of devices, the delamina-tion of parylene from the PCB occurred, causing the volumeto enlarge to form a void, which eventually becomes a gasbubble due to permeation of gases through parylene, asshown in Fig. 8.

In this scenario, it is assumed that pressure is changingquickly relative to permeation and dilution in the liquidsuch that there is no mass changing in the bubble.Because the bubble can compress so easily compared tothe oil, it is also assumed that the oil has infinite bulkmodulus for simplicity. So,

V 1−V 2−Vb þ V f unnel ¼ Voil ð15Þ

If Penv. = Poil = P0, then V1 = V2 = 0, and a bubble of radiusb0 is observed. So

Vb0 ¼ V f unnel−Voil ¼ Vb þ V 2−V 1 ð16Þ

Assuming a spherical bubble, it is known that

Vb0 ¼4

3πb3 þ c2 Penv:−Poilð Þ−c1 Poil−P0ð Þ ð17Þ

where each ci is defined as in Equation (10). The Laplacepressure of a bubble says that,

Pb ¼ Poil þ 2r

bð18Þ

Assuming a constant temperature, then

nRT ¼ VbPb ¼ Vb0Pb0 ¼4

3πb30

� �P0 þ 2γ

b0

� �ð19Þ

and thus

4

3πb3 ¼ nRT

Poil þ 2γb

ð20Þ

Assuming a fixed value of P0, Penv. is swept and Eqs. (17)and (20) are solved simultaneously with a numerical solverusing the variables (b, Poil). Choice of P0 in practice mostlyonly changes the constant offset of Poil versus Penv. for therange of values inspected.

One of the pressure sensor packages was found to have abubble. The device’s pressure response was examined at mul-tiple times. Afterwards the package was sliced open, leavingthe sensor in oil but otherwise exposed to air, and examinedagain. The bubble can be seen in Fig. 9. The opened packageis shown in Fig. 10.

The results of the experiments are shown in Fig. 11. Formodeling purposes, P0 is assumed to be 99 kPa. An effec-tive circular outer membrane of 1.3 mm radius is assumed,which is approximately the area between the silicone postsused for this device. The square silicon membrane of thesensor is measured to be 9 μm thick and 375 μm wide.Packaging was 30,000 cSt silicone oil and PA-D thickness

Fig. 7 Schematic to create concave surface of the parylene-on-oilpackaging. When oil expands due to the temperature increase,concavity provided by the posts allows the parylene coating toaccommodate easily

Fig. 8 Funnel model representation of a parylene-on-oil package with abubble in the oil.When a bubble is present, the relative sensitivity Sr losesmeaning as the slope of sensed pressure to control pressure is notconstant. A numerical method to explain a bubble’s effect on relativesensitivity is proposed. a The starting condition, where theenvironmental pressure and the oil pressure equal the sensor chamberpressure so that neither membrane deflects, and where the bubble size ismeasured by observation. b The environmental pressure increases so as tocause deflections in both membranes and shrinkage of the bubble

Biomed Microdevices (2016) 18: 66 Page 7 of 10 66

of 27 μm. The bubble radius at room pressure b0 is mea-sured to be 0.45 mm.

As shown in Fig. 11, the qualitative non-linear behaviorfrom the presence of a bubble is predicted by the modelquite well. Although a hysteresis is observed, which cannotbe replicated by this non-dynamical model, it is hypothe-sized that some mass exchange inside the bubble occurred.It is also found that repeated measurements of a sensor un-der vacuum would cause the bubble to increase in size and,hence, the offset, consistent with the hypothesis that the voidinduced by the vacuum would be filled by air when broughtup to atmosphere.

After the bubble was observed, the parylene package wascut open to release the bubble. As expected, the followingexperiments without the bubble showed that the pressure sen-sor output was indistinguishable from that of an unmodifieddevice. This proves that the bubble alone caused the loss ofpressure transduction to the sensor. Thus, the silicone oil mustbe free of bubbles for accurate pressure sensing.

6.3 Biofouling sensitivity estimation

As stated earlier, the larger exterior membrane means that, forthe same thickness of biofouling, the effect on the reduction ofsensitivity is less than if the pressure sensor was directly

covered with parylene. In other words, the sensitivity drift ispredicted to be negligible with the parylene-on-oil packaging.It is imperative to understand that the sensitivity drift can bemistaken as a large offset drift if there is typically a largepressure difference across the piezoelectric membrane. Onemight try to recalibrate the device by updating the constantoffset only, when it is appropriate to update the assumed sen-sitivity. However, estimating sensitivity drift over time isharder than for offset drift because it requires multiple pointcalibration. The problem with drift is that it is impossible toperfectly predict over time, inevitably leading to accuracydegradation. The larger the drift, the harder it is to estimateto the same absolute level of precision. Thus suppressing drift,especially sensitivity drift if possible, is a fruitful strategy. Thetypical error one should expect is

ð21Þ

Let us estimate an upper bound on tolerable sensitivity drifthere for the case of blood pressure monitoring. The high end ofblood pressure is roughly 100 mmHg above atmosphere andthe normal accuracy/resolution required for blood pressuremonitoring is typically 1 mmHg or better. If P0 is 1 atm, evenignoring DC offset drift, the sensitivity drift must be <1 %. Forthis reason we believe multiple recalibrations and/orbiofouling-preventing schemes cannot achieve this tight toler-ance. Instead we predict that an exterior membrane which me-chanically eliminates sensitivity drift will be a better solution.

For example, let us estimate the sensitivity drift of aparylene-on-oil packaged pressure sensor versus a devicewithout oil directly coated with the same thickness of

Fig. 9 A packaged MPL115A1 sensor was observed to have a bubblepresumably due to parylene delamination and gas permeation

Fig. 10 The package in Fig. 9 was cut open to confirm the fullfunctionality of the original pressure sensor

Fig. 11 A packaged MPL115A1 sensor was observed to have a bubblepresumably due to parylene delamination and gas permeation. Pressureresponses from before and after the packaging was opened are shownhere. The theoretical pressure reading with a bubble is in goodagreement with the measurements. After the package is cut open, thepressure sensor behaves as if unmodified, confirming that thenonlinearity is caused by the bubble alone

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ΔPmeas ¼ Penv:−P0ð ÞΔSr þΔPDCo f f set

parylene. Relative sensitivity of parylene-only depositionpackaging of membranes with thin gels are modeled by theinverse change of flexural rigidity because there is no slippagebetween the layers of a multilayer plate (Ventsel andKrauthammer 2001; Pister and Dong 1959; Choi et al.1999). Assume that the parylene membrane on the oil is3 mm wide square, representing the footprint of a typicalcommercial sensor, and a 10 μm thick layer of PA-D for bothcases. Assuming a 100 μm thick layer of biofouling withEbiofoul = 6 MPa (Quaglini et al. 2005), the parylene-on-oilpackaged device exhibits effectively no sensitivity drop orsensitivity drift according to our model. Meanswhile, aparylene-only packaged device exhibits an initial drop to58 % relative sensitivity will further drift to 47 % relativesensitivity due to the 100 μm biofouling, i.e. a proportionalsensitivity drift of 18 %. Here, the silicon membrane is a352 μm wide square. Other inputs in this model are EPA-

D = 2.8 GPa, EGel = 1 kPa, ESi = 150 GPa, νPA-

D = νGel = 0.4, νSi = 0.3, tSi = 9 μm, and tGel = 5 μm.

7 Conclusion

Exploiting the unusual fact that CVD parylene can depositdirectly on oil, a parylene-on-oil packaging scheme was con-ceived to achieve a long-term lifetime of implantable pressuresensors. Silicone oil protects the sensor from chemical corro-sion due to water or electrolytes, and parylene encapsulatesthe oil to protect the sensor from biofouling. Because of in-creased surface area of the outer membrane, the protectivebenefits of thick parylene can be used without sacrificing sen-sitivity, while achieving protection from biofouling. A modelto predict relative sensitivity of parylene-on-oil packaging ispresented under the presumption that, with calibration, a con-stant offset would be compensated anyway. A model to ex-plain sensor behavior with the presence of a bubble is alsopresented, confirming that bubbles will cause failure of satis-factory pressure transduction. Antibiofouling by both chemi-cal resistance to biofouling and active removal of biofouling isa field of active study by itself, and there is a lack of aneffective approach now. On the contrary, our proposedparylene-on-oil packaging for pressure sensor protection ispromising to eliminate many of the negative effects of bio-fouling despite its presence, which we believe is a more ro-bust, simpler solution (Hsu 2014; Xu et al. 2015;Sankaranaravanan et al. 2008).

We have proven the feasibility of the packaging concept.The experimental results presented in Table 1 also show thatparylene-on-oil packaging has the capability to protect a pres-sure sensor much longer than previously achieved. Althoughthe weakest spot in the current demonstration was where thewires were joined to the PCB, our vision of a wireless devicewill be free of wire problems.

Nevertheless, future works with animal studies should beinvestigated to verify the virtues of this packaging method.

Acknowledgments The authors would like to thank Mr. Trevor Roperfor his help on all the equipment at the Caltech MEMS Lab.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict ofinterest.

Human and animal rights This article does not contain any studieswith human participants or animals performed by any of the authors.

References

N. Binh-Khiem, K. Matsumoto, I. Shimoyama, Tensile film stress ofparylene deposited on liquid, Langmuir. Am. Chem. Soc. 26(24),18771–18775 (2010). doi:10.1021/la102790w

N. Binh-Khiem, K. Matsumoto, I. Shimoyama, Porous parylene and ef-fects of liquid on parylene films deposited on liquid. IEEE MEMS,111–114 (2011). doi:10.1109/MEMSYS.2011.5734374

J. H. C. Chang, Wireless parylene-based retinal implant, Ph.D. Thesis,California Inst. of Tech. (2013)

J. H. C. Chang, Y. Liu, D. Kang, Y.-C. Tai, Reliable packaging forparylene-based flexible retinal implant. Digest Tech. PapersT r a n s d u c e r s , 2 6 1 2 – 2 6 1 5 ( 2 0 1 3 ) . d o i : 1 0 . 1 1 0 9/Transducers.2013.6627341

S. Choi, J. Hutchinson, A. Evans, Delamination of multilayer thermalbarrier coatings. Mech. Mater. 31(7), 431–447 (1999)

I. Clausen, T. Glott, Development of clinically relevant implantable pres-sure sensors: perspectives and challenges. Sensors 14(9), 17686–17702 (2014). doi:10.3390/s140917686

P. Cong, W. H. Ko, D. J. Young, Wireless batteryless implantable bloodpressure monitoring microsystem for small laboratory animals.IEEE Sensors J . 10(2), 243–254 (2010). doi:10.1109/JSEN.2009.2030982

W. F. Gorham, A new, general synthetic method for the preparation oflinear poly-p-xylylenes, journal of polymer science part A-1: poly-me r chem i s t r y, 4 3027–3039 (1966 ) . do i : 10 . 1002/pol.1966.150041209

A. Homsy, E. Laux, L. Jeandupeux, J. Charmet, R. Bitterli, C. Botta, Y.Rebetez, O. Banakh, H. Keppner, Solid on liquid deposition, a re-view of technological solutions. Microelectronic Eng. 141, 267–279(2015). doi:10.1016/j.mee.2015.03.068

L. Hsu, Development of a low-cost hemin-based dissolved oxygen sensorwith anti-biofouling coating for water monitoring. IEEE Sensors J.14(10), 3400–3407 (2014). doi:10.1109/JSEN.2014.2332513

G. Jiang and D. D. Zhou, in Implantable neural prostheses 2, ed. By D.D.Zhou and E. Greenbaum, Techniques and Engineering Approaches.(Springer Science & Business Media, LLC, 2010). p. 27–61 doi:10.1007/978-0-387-98120-8_2

T. Kan, H. Aoki, N. Binh-Khiem, K. Matsumoto, I. Shimoyama,Ratiometric optical temperature sensor using two fluorescent dyesdissolved in an ionic liquid encapsulated by parylene film. Sensors13(4), 4138–4145 (2013). doi:10.3390/s130404138

H. Keppner, and M. Benkhaïra, Method for producing a plastic mem-brane device and the thus obtained device.WO/2006/063955 (2004)

A. Koutsonas, P. Walter, G. Roessler, N. Plange, Implantation of a noveltelemetric intraocular pressure sensor with glaucoma (ARGOS

Biomed Microdevices (2016) 18: 66 Page 9 of 10 66

study): 1-year results. Invest. Opthamol. Vis. Sci. 56(2), 1063–1069(2015). doi:10.1167/iovs.14-14925

K. B. Liland, K. Eidnes, K. Bjorneklett, S. Hvisdten, Measurement ofsolubility and water content of insulating oils for HV XLPE cableterminations. IEEE Electrical Insulation (2008). doi:10.1109/ELINSL.2008.4570264

B. Lutz, Z. Guan, L. Wang, F. Zhang, Z. Lü, Water absorption and watervapor permeation characteristics of HTV silicone rubber material.Electrical Insulation (ISEI) 478-482 (2012). doi:10.1109/ELINSL.2012.6251514

S. J. A. Majerus, P. C. Fletter, M. S. Damaser, S. L. Garverick, Low-power wireless micromanometer system for acute and chronicbladder-pressure monitoring. IEEE Trans. Biomedical Eng. 58(3),763–767 (2011). doi:10.1109/ TBME.2010.2085002

B. Nguyen, E. Iwase, K. Matsumoto, I. Shomoyama, Electrically drivenvarifocal micro lens fabricated by depositing parylene directly onl iqu id . IEEE MEMS, 305–308 (2007) . do i :10 .1109/MEMSYS.2007.4433059

K. S. Pister, S. B. Dong, Elastic bending of layered plates. Proc ASCE JEng Mech Div 84(1–10) (1959)

V. Quaglini, S. Mantero, T. Villa, Mechanical properties of breastperiprosthetic capsule and the correlation to capsule contracture. J.of App. Biomat. & Biomech. 3(3), 184–191 (2005)

S. Sankaranaravanan, S. Cular, V. Bhethanabotla, and B. Joseph,Subramanian flow induced by acoustic streaming on surface-acoustic-wave devices and its application in biofouling removal: acomputational study and comparisons to experiment. 77(6), 06683(2008) doi:10.1103/PhysRevE.77.066308

W. K. Schombur, Introduction to microsystem design (Springer-Verlag,Berlin Heidelberg, 2011)

SCS Parylene Properties, (Specialty Coating Systems, 2007), http://www.physics.rutgers.edu/~podzorov/parylene%20properties.pdf.Accessed 9 Sept 2015

A. Shapero, Y. Liu, Y.-C. Tai, Parylene-on-oil packaging for implantablepressure sensors. IEEE MEMS, 403–406 (2016). doi:10.1109/MEMSYS .2016.7421646

Shin-Etsu Silicone, Silicone Fluid, KF-96, (performance test results,2004), http://www.silicone.jp/e/. Accessed 1 Aug 2015

E. Ventsel, T. Krauthammer, Thin plates and shells, theory, analysis, andapplications (Marcel Dekker, Inc, New York, 2001), pp. 231–232

P. Wang, S. J. A. Majerus, R. Karam, B. Hanzlicek, D. L. Lin, H. Zhu, J.M. Anderson, M. S. Damaser, C. A. Zorman, W. H. Ko, Long-termevaluation of a non-hermetic micropackage technology for MEMS-based, implantable pressure sensors. Digest Tech. PapersT r a n s d u c e r s , 4 8 4 – 4 8 7 ( 2 0 1 5 ) . d o i : 1 0 . 1 1 0 9/Transducers.2015.7180966

W. Wessel, Fluid pressure sensor, particularly diesel engine injectionpump pressure sensor. US4430899 A (1984)

C. Xu, X. Hu, J. Wang, Y. M. Zhang, X. J. Liu, B. B. Xie, C. Yao, Y. Li,X. S. Li, Library of antifouling surfaces derived from natural aminoacids by click reaction. ACS Appl. Mater. Interfaces 7(31), 17337–17345 (2015). doi:10.1021/acsami.5b04520

L. Yu, B. Kim, E. Meng, Chronically implanted pressure sensors: chal-lenges and state of the field. Sensors 14(11), 20620–20644 (2014).doi:10.3390/s141120620

66 Page 10 of 10 Biomed Microdevices (2016) 18: 66