A WIRELESSLY-ACTIVATED PARYLENE ELECTROTHERMAL VALVE FOR
MAPPING BRAIN FUNCTION IN FREELY MOVING SUBJECTS
Po-Ying Li1, Tina K. Givrad2, Daniel P. Holschneider2,3, Jean-Michel I. Maarek2, and Ellis Meng2
Department of Electrical Engineering, University of Southern California, Los Angeles, California, USA
2
Department of Biomedical Engineering, University of Southern California, Los Angeles, California, USA
3
Department of Psychiatry, Neurology, Cell and Neurobiology, University of Southern California, Los Angeles,California, USA
1weight) for implantation in genetically engineered mice (~40 g) andmaintains the ability to open quickly for on-demand release of aradiotracer.

ABSTRACTThe first normally-closed Parylene valve operating onelectrothermal principles for rapid and wireless drug delivery was
designed, fabricated, modeled, and tested. This valve is a key
component of an implantable microbolus infusion pump (MIP) for
neuroimaging in freely-moving untethered animals.
This
low-power, lightweight MEMS valve enables an MIP suitable forstudying functional brain activation in genetically engineered miceby replacing a large conventional solenoid valve used previously inlarger animals.

INTRODUCTION
In traditional neuroimaging, to avoid movement artifacts
during data acquisition, subjects need to be immobilized oranesthetized. This is one of the major constraints on neuroimaging
in animals which prevents study of fundamental behaviors linked to
locomotor activities and introduces additional variables of stress oranesthetic agent that may confound meaningful interpretation. To
acquire detailed understanding of the neural mechanisms
underlying fundamental mammalian behaviors, such as aggression,
mating, feeding, and fear, new techniques are required.
An implantable microbolus infusion pump (MIP) (Fig. 1)
consisting of a drug reservoir, tuned inductive coil, catheter, andvalve has been introduced for drug delivery in rats [1,2]. The MIP
has allowed, for the first time, cerebral perfusion mapping in
conscious freely-moving small animals. The remotely triggered
valve initiates rapid release of a radioactive tracer from apressurized reservoir directly into systemic circulation followed byrapid euthanasia. Regional cerebral blood flow is assessed using
autoradiography. However, to apply the same drug delivery scheme
to smaller animals, such as mice, a key requirement of the MIP
system is the total weight and size of the implant which must be lessthan 3 grams and allow for subcutaneous implantation in a 40-gram
mouse. In addition, the valve footprint should match the innerdiameter of the catheter (330 or 500μm). Current technology inimplantable drug delivery in small animals (constant rate infusionpump) is unable to achieve the rapid injection necessary to prevent
nonspecific tracer distribution. A new valve is required that reduces
the overall weight and size of the MIP (from 32 g to <3 g total

Figure 1: Miniature bolus infusion pump for neuroimaging in mice.
Normally-closed MEMS electrothermal valves capable ofrapid opening provide a potential solution for the new MIP system.
Previously, electrothermal valves have been developed but only oneof these is suited for implantable drug delivery (Table 1) [3-8]. Thisvalve consists of a resistive metallic membrane (Pt/Ti/Pt) suspended
over a drug reservoir that opens when an applied current melts themembrane. However, melting the metallic membranes requires
significant power to produce the necessary temperature. Here, we
use a Parylene C/Pt composite membrane since Parylene C can bethermally degraded at much lower temperature (125-200°C) [9] andcan form large mechanically robust membranes for larger effective
valve opening area (330-500 µm in diameter).

Table 1: Comparison of the our valve with valves reported in research literature.
Membrane Materials
Membrane Dimension
L x W x T (µm)
Thermal Element Materials
Thermal Element Thickness (Å)
Mass Transport MechanismMax. Pressure (kPa (psi))
Melting Temperature (ºC)
Opening Power (mW)
Applied Voltage (V)Applied Current (mA)
Opening Time (ms)Energy (mJ)
Biocompatibility
Delivered Material(Solid/Liquid/Gas)

Maloney [3]Pt/Ti/Pt

Cardenas-Valencia [4]SiNx

Mueller [5]Doped Silicon

Hong [6]Un-crosslinked SU-8

Guerin [7]PE/PET Film

McDonald [8]PDMS

Our Device
Parylene

50 x 50 x 0.01

3000 x 3000 x 3

N/A x N/A x 50

N/A x N/A x 50

N/A x N/A x 35

100 x 60 x 20

ø500 x 10 (thick)Pt/Ti/Pt10/100/10
Diffusion
N/A
1770
2250
N/A
1000
0.010.025
Yes

Pt/Ti
300/90Pressure Driven
500.0 (72.5)
700
16000
70
N/A
20320
No

Doped Si
500000Pressure Driven
20684.3 (3000)
1400
300
N/A
N/A
0.1
30
No

Ni
50000
Pressure Driven
96.5 (14)
50
0.08
0.7
N/A
1000
0.08
No

Cu
N/A
Pressure Driven
200.0 (29)
120
400
1.5
N/A
1200
400
No

Pt
N/A
Pressure Driven
N/A
N/A
7.5
420
N/A
0.02
150
NoPt
1000
Pressure Driven
689.4 (100)
125
25.2
3.6
7100
2.52
Yes

Solid/Liquid

LiquidGas

Gas

LiquidLiquid

Liquid0-9640024-7-7/HH2008/$20©2008TRF

32

Solid-State Sensors, Actuators, and Microsystems Workshop
Hilton Head Island, South Carolina, June 1-5, 2008

Table 2: Valve design parameters.
Valve ID

33020

50020

p0 a 4⎛w ⎞= 0.488 ⎜ max ⎟64 D⎝ t ⎠

50040

330
20
1780

500
203880(3)Nonlinear FEM analysis was also performed (Fig. 3). The results
indicated that the maximum stress of the Pt element under 1 atmpressure (peak under normal operation) is 1.53GPa which is lessthan its tensile strength (1.83GPa). Thus, the electrical connections
are expected to survive pressurized conditions during radiotracer
loading. The nonlinear model results showed good agreement withload deflection experiments (composite membrane) obtained using
a custom pressure testing setup (Fig. 4).

LayoutOccupied Diameter (µm)
Element Line Width (µm)
Total Element Length(µm)

3500402380DESIGNThe electrothermal drug delivery valve consists of anelectron-beam evaporated platinum thin film platinum resistive
element embedded in a flexible Parylene C membrane (10 μm) (Fig.
2 and Table 2). Parylene further simplifies the valve design by
obviating the etched silicon membrane support. The valve issituated in the lumen of a catheter and two contact pad flaps arewrapped along the catheter for connection to control circuitry (Fig.
2c). Current is applied to initiate Joule heating to thermally degradeor melt the Parylene membrane. When the electrical andmechanical connections are broken, the pressurized reservoir drives
rapid release of fluids through the catheter and into the venous
circulation. This convenient format can be implemented in many
microfluidic applications where an inexpensive, disposable valve isrequired.

Figure 3: Finite element analysis using COSMOSWorks®: (a)nonlinear FEM model, (b) mesh, (c) vertical displacement (1 atm),and (d) stress distribution (1 atm).

Figure 2: Parylene electrothermal drug delivery valve: (a) device
layout, (b) close-up of valve element, and (c) illustration ofoperation principle of the valve.
Modeling
To ensure that the Pt element can survive the instantaneous
peak pressure from reservoir (1 atm), membrane mechanicalperformance was verified using both large deflection approximation(Parylene only) and nonlinear FEM models (Parylene/Pt/Parylene).
First, in the large deflection theory [10], the nonlinear
strain-displacement relations can be expressed as∂u 1 ⎛ ∂w ⎞εx = + ⎜ ⎟∂x 2 ⎝ ∂x ⎠2∂v 1 ⎛ ∂w ⎞+ ⎜⎟∂y 2 ⎝ ∂y ⎠2εy =γz =∂v ∂u ∂w ∂w++∂x ∂y ∂x ∂yFigure 4: Comparison of experimental data with nonlinear FEM
model and large-deflection approximation.

FABRICATION
The valves were constructed using standard microfabrication
techniques. The fabrication began with a 3 inch Si wafer with nativeoxide to facilitate Parylene C release. First, Parylene layer (5 μmthick) was deposited (Fig. 5A). This is the first layer of theParylene/metal/Parylene sandwich. Two layers of photoresist(AZ1518 and AZ4400) were spun to create an undercut for Pt liftoff(Fig. 5B). Then liftoff lithography was performed and a 1000 Å Pt
film was e-beam evaporated. Following liftoff, the resistive
element and contact pad were defined (Fig. 5C). The top Parylenelayer (5 μm thick) was then deposited (Fig. 5D). To reveal thecontact pad openings, a thick photoresist layer (8 μm of AZ4400)
was patterned as a mask for reactive ion etching (Fig. 5E). The
Parylene over the contacts was removed by oxygen plasma. Thenthe photoresist was stripped and thermally annealed in vacuum withnitrogen backfill (200°C for 2 days) (Fig. 5F). The entire wafer wasimmersed into DI water to release the valves and the individual
devices were manually cut from the wafer (Fig. 5G).

(1)

where εx, εy, and εz and u, v, and w are stresses and displacements inx, y and z directions, respectively. The corresponding governing
differential equations are⎡⎛ ∂ 2 w ⎞ 2 ∂ 2 w ∂ 2 w ⎤∂ 4φ
∂ 4φ
∂ 4φ
⎢⎜⎥ and++=2E⎟ − 22∂x 4∂x 2 ∂y 2 ∂y 4⎢⎣⎝ ∂x∂y ⎠ ∂x ∂y ⎥⎦∂4w∂4w∂ 4 w t ⎡ p ∂ 2φ ∂ 2 w ∂ 2φ ∂ 2 w∂ 2φ ∂ 2 w ⎤+2 2 2 + 4 = ⎢ + 2 2 + 2 2 −2
⎥
∂x 4
∂x ∂y
∂y∂x ∂y∂x∂y ∂x∂y ⎦D ⎣ t ∂y ∂x(2)where φ is the stress function, E is Young’s modulus, t is thethickness of the plate, D is the flexural rigidity, and p is the appliedpressure. By using the minimum strain energy method, the solution
for a clamped thin circular plate subject to a uniform load p0 is33

were obtained. Then the valve element temperature can be
estimated by using the following equation and the experimentally
determined TCR:
T = T0 +R (T ) − R (T0 )α R (T0 )(5)

The valve opening experiments were performed in both air andwater. In air, the valve opening power and current were obtained byapplying constant current starting from 1 mA and increasing insmall increments; the current corresponding to valve opening wasrecorded. Corresponding opening power values were calculated.
Current ramping was also examined for valve operation in water.
Five ramping rates were tested to obtain reliable valve opening. The
devices were evaluated by using a laser-machined test fixture toallow rapid electrical connections and facilitate visual observationof the valve. The entire process was monitored by a compound
microscope connected to a computer-controlled CCD camera
capable of recording time lapse images.

RESULTS AND DISCUSSIONTCR calibration experiment results are presented in Fig. 7a. A
typical TCR for our e-beam deposited thin film Pt heater was 16.3 x
10-4/°K which is lower than that expected for bulk Pt TCR (39.2 x
10-4/°K). This TCR value was applied to the OHT measurements topredict the Pt heater temperature at different applied currents (Fig.
4b). To prevent destructive thermal degradation of the device under
test, the OHT experiments were performed at currents below
opening values and the results were extrapolated to higher current
ranges by using a 2nd-order polynomial curve fit. As depicted inFig. 4b, a valve opening current between 10 to 15 mA was expected.

Figure 5: Fabrication process flow for the electrothermal valve.
Valve Assembly
The valve is situated in the lumen of a catheter and two contact
pad flaps are wrapped along the catheter for connection to control
circuitry (Fig. 6). To package the valve, the device was first
sandwiched between two catheter segments and two laser-cut
double-sided adhesive rings (Fig. 6a). Then conductive epoxy wasused to secure electrical wires to the contact pads (150°C for 15hours) (Fig. 6b and d). Finally, the joined assembly wasstrengthened with a bead of epoxy (Fig. 6c and e). The assembly
process was performed under a stereo microscope.

(a)(b)
Figure 7: Representative valve electrothermal calibration curves(a) temperature dependence and (b) overheat temperature.
Valves were successfully opened in air (constant current) andwater (current ramping) (Fig. 8-10). For constant current, opening
current and power decreased with increasing resistance. The stagesof valve opening (in water) were observed in real-time while
simultaneously tracking the resistance by using current ramping.
Five ramping rates (0.025 to 2 mA/sec) were tested to obtain the
optimal opening rate (Table 3). Reliable valve opening wasobtained for ramping rates less than 0.1 mA/sec.

Figure 6: Assembly process for the electrothermal valve: (a)exploded view of components, (b) conductive epoxy for wireattachment, (c) epoxy bonding of the assembly, (d) wires attached tothe contact pad by conductive epoxy, and (e) packaged device.

EXPERIMENTAL METHOD
Benchtop Testing
The temperature coefficient of resistivity (TCR), overheattemperature (OHT), and valve opening power of the Parylene C
electrothermal valve were determined in benchtop experiments.
TCR is an important parameter to predict Pt heater resistance atdifferent temperatures. The temperature dependence of Pt isapproximately linear over the range of interest and can be express as
R (T ) = R (T0 ) ⎡⎣1 + α (T − T0 ) ⎤⎦(4)
where R(T) is the resistance at temperature T, To is an appropriate
reference temperature, and α is the TCR. In addition, the OHT
allows the temperature of the resistive element to be calculated fromits resistance. Pt element resistances for different applied currents

Figure 8: Valve opening (in air): (a) an open valve (15 mA), (b)magnified view of the edge of the valve orifice, and (c) valve
opening current and power to resistance relationship.
34

CONCLUSION
We successfully developed a disposable, low-power Parylene
C MEMS valve for neuroimaging applications. The design,modeling, fabrication, and benchtop characterization wereperformed and investigated. TCR and OHT experiments allowed
prediction of the temperature of the heater and determination of theappropriate current to apply to open the valve. Opening powers of
25-50 mW were obtained in air and reliable valve opening in waterusing current ramping rate of 0.1 mA/sec was obtained. Further
reduction in power consumption and optimization of valve
performance is planned. Also, additional experiments will evaluate
the performance of the valve in the presence of the radiotracer agent
and in vivo.

Figure 9: Valve opening (in water). Left: real-time response of thevalve.
Right: (a-d) time lapse images of valve opening
corresponding to resistance measurement events in the left plot.

ACKNOWLEDGEMENTS
This work was funded in part by the NIBIB (1 R01
NS050171). The authors would like to thank Dr. Donghai Zhu, Dr.
Tuan Hoang, Mr. Neil Sardesai, and members of the Biomedical
Microsystems Lab at University of Southern California.

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Figure 10: Current ramping rate. The inset shows a close up of the0.1 mA/sec waveform.
Table 3: Optimization results for current ramping testing in water.
RampingRate(mA/sec)
0.025
0.1
0.20.42.0

Valve ID 33020
Not
OpenOpenO
OX
OX

Valve ID 50020
Not
OpenOpenOO
X
XX

Valve ID 50040
NotOpenOpenOOOX
X

NEUROIMAGING
Valve integration into the new MIP design has commenced andwireless operation has already been demonstrated in the mouseemitter coil cage (Fig. 11a). Neuroimaging studies are planned andautoradiographic brain slices and optical density analysis will beobtained. Fig. 11b compares the dimensions of the MIP and amouse.

Figure 11: Neuroimaging: (a) in vivo testing setup in which the MIP
is powered by inductive power transfer from a primary coilwrapped around the experimental cage, (b) relative size of the MIP
and a mouse.

35