PARYLENE ELECTROTHERMAL MEMS DRUG
DELIVERY VALVE
Po-Ying Li, Daniel P. Holschneider, Jean-Michel I. Maarek, and Ellis Meng
Department of Biomedical Engineering
University of Southern California
1042 Downey Way, DRB-140
Los Angeles, CA 90089-1111
Introduction
In the past decade, the applications of Parylene in
microelectromechanical systems (MEMS) devices have attracted significant
attention especially for implantable drug delivery systems that integratesensing, pumping, and valving1,2. These advanced drug delivery systems
exploit the excellent mechanical and electrical properties of Parylene C byutilizing it as primary structural material in MEMS technology. An
implantable microbolus infusion pump (MIP) (Figure 1) consisting of a drug
reservoir, tuned inductive coil, catheter, and valve has been introduced for
drug delivery in rats3,4. By inductively triggering the valve, a radioactive
tracer is delivered into the circulation to enable rapid injection of a radiotracer
for neuroimaging of brain blood flow in freely-moving untethered animals. A
key requirement of the drug delivery system for mouse applications is the total
weight and size of the implant; the weight must be less than 3 grams and thesize must allow for subcutaneous implantation in a 40-gram mouse. Inaddition, the valve footprint should match the 330 µm inner diameter of thecatheter. A MEMS Parylene C-based electrothermal valve is explored as a
low-power, light-weight solution for the MIP drug delivery system.

Figure 2. Parylene electrothermal drug delivery valve: (a) the device, (b) theheater, and (c) the operation principle of the valve.
Fabrication.
The valves were constructed using standard
microfabrication techniques. First, Parylene C (5 µm in thickness) wasdeposited on a 3 inch silicon wafer (Figure 3A). This is the first layer of theParylene C/metal/Parylene C sandwich. Then liftoff lithography wasperformed and a 1000 Å thick platinum film was e-beam evaporated.
Following liftoff, the heater and contact pad of the valve were defined (Figure3B). The top Parylene layer (5 µm in thickness) was then deposited (Figure3C). To completely open the contact pad, a thick photoresist layer (8 µm ofAZ4400) was patterned as a mask for reactive ion etching (RIE) (Figure 3D).
The Parylene C over the contacts was removed by oxygen plasma. Then thephotoresist was stripped in acetone (Figure 3E). The entire wafer wasimmersed into DI water to release the Parylene C membrane and theindividual devices were manually cut from the wafer (Figure 3F). Finally, thevalves were thermally annealed in vacuum under nitrogen backfill conditions(2 days at 200 ºC).

Figure 1. Miniature infusion pump for neuroimaging in mice.
Many groups have developed electrothermal valves for similar drugdelivery applications5,6. These valves resemble electrical fuses and consist ofa resistive heating element (platinum or gold) or metal/silicon nitride
composite as a membrane. When electrical power is applied, the heater melts
the thin film membrane and opens the valve. However, melting themembranes requires significant power to produce the necessary temperature.
Here, we propose to use Parylene C as the heater-supporting membranematerial in our electrothermal valve design. Parylene can be thermally
oxidized and degraded at much lower temperatures (between 125°C and200°C)7 and is expected to enable low-power valves for use in wirelessimplants. In addition, this concept can adapted for the development ofreconfigurable microfluidic devices.
Experimental
Design. The electrothermal drug delivery valve (Figure 2a) consists ofan electron-beam evaporated platinum thin film heater embedded in the centerof a 10 µm thick flexible Parylene C membrane. Figure 2b shows theserpentine pattern of the platinum heater (with a 20 µm wide wire confined in
a 330 µm diameter circular area). Two contact pads (1.5 mm x 3 mm)
connecting to the resistive element allow connection to external wires of thecontrol circuitry. The meandering pattern of the heater was selected tomaximize resistance of the heating element compared to the electricalcontacts. When current is applied, most of the electrical power is consumed
by this heater resistor and converted into thermal energy. This heat elevates
the temperature of the Parylene C around the heater and thermally degrades
the Parylene C membrane. The thermally-generated opening in the Parylene C
membrane creates fluid flow path for the pressurized contents of the reservoir
through the catheter and into the venous circulation (Figure 2c).

Figure 3. Simplified process flow for the Parylene C electrothermal drugdelivery valve.
Benchtop Testing. The resistance, temperature coefficient of resistivity,
overheat temperature, and valve opening power of the Parylene C
electrothermal drug delivery valve were determined in benchtop experiments.
To predict the theoretical resistance of the heater, sheet resistance of thin film
platinum coated on a soda lime glass slide was first measured. The theoreticalresistance of a resistor can be calculated byl(1)
R = Rsw

where R is the heater resistance, Rs is the sheet resistance, l is the length of theheater, and w is the width of the heater. The resistances of the fabricatedvalve devices were also measured and compared to the theoretical values.
Temperature coefficient of resistivity (TCR) is an important parameter topredict Pt heater resistance at different temperatures. The temperaturedependence of Pt is approximately linear over the range of interest and can be
express as(2)R(T ) = R(To )[1 + α (T − To )]where R(T) is the resistance at temperature T, To is an appropriate referencetemperature, and α is the temperature coefficient of resistivity. The
temperature calibration curve was experimentally determined by placing thePolymer Preprints 2008, 49(1), 941

device in a temperature-controlled environmental chamber and recording theresistance at different temperature setpoints. The measurements weresubstituted into equation (2) to obtain TCR. In addition, the overheattemperature (OHT) allows the temperature of the heater to be calculated fromits resistance. Heater resistances for different applied currents were obtained.
Then the heater temperature can be estimated by using the following equationand the experimentally determined TCR:
(3)
R (T ) − R (To )T = To +αR (To )The valve opening power and current were obtained by applying
constant current starting from 1 mA and increasing in small increments; thecurrent corresponding to Parylene C membrane valve opening was recorded.
Corresponding opening power values were calculated. The devices wereevaluated by using a laser-machined test fixture to allow rapid electricalconnections and facilitate visual observation of the valve. The entire process
was monitored by a compound microscope connected to a computercontrolled CCD camera capable of recording time lapse images.
Results and Discussion
Benchtop Testing. The sheet resistance measured from the e-beam
evaporated Pt on the soda lime glass slide was 2.24±0.12 Ω/□ (mean±SE,n=5). The corresponding theoretical resistance of the heater based onequation (1) was 199.22 Ω. The measured value was 174.9±12.62 Ω(mean±SE, n=10) which is slightly lower than expected.
Figure 4a shows the results of TCR calibration experiment. A typicalTCR for our e-beam deposited thin film Pt heater is 16.3 x 10-4/°K which islower than that expected for bulk Pt TCR (39.2 x 10-4/°K). This TCR value
was applied to the OHT measurements to predict the Pt heater temperature atdifferent applied currents (Figure 4b). To protect destructive thermal
degradation of the device under test, the OHT experiments were performed atlower currents and the results were extrapolated to higher current ranges byusing a 2nd-order polynomial curve fit. As depicted in Figure 4b, the valve
opening current is expected to be between 10 to 15 mA for Parylene C.

(a)(b)
Figure 4. Typical heater responses for (a) TCR and (b) OHT experiments.
Figure 5 shows an open Parylene C electrothermal valve after theapplication of 15mA in air. A further magnified view (Figure 5b) shows theedge of thermally generated valve orifice. Four devices were used for valve
opening experiments (Figure 6). Both valve opening current and power
decrease with increased heater resistance. This result indicates a longer andthinner heater will improve power consumption. Measured opening currents
were 7-20 mA and the corresponding calculated power consumption wasbetween 25-50 mW.

Figure 6. Valve opening current and power to heater resistance relationship.
Valve Assembly. The Parylene C drug delivery valve needs to beassembled in the path of the catheter to incorporate it into the microbolus
infusion pump system. The electrical connections to control circuitry wasestablished by using thin wires adhered with conductive epoxy (150°C for 15hours). Then the valve was sandwiched between two lengths of catheter andsecured with epoxy. The flexible Parylene C film allows the contact padregions to be folded back over the catheter to minimize the overall valve
footprint. The assembly process was performed under a stereo microscope(Figure 7).

Figure 7. Device assembly for the Parylene MEMS drug delivery valve.
Conclusion
We successfully developed a disposable, low-power Parylene C MEMS
valve for drug delivery application. The design, fabrication, and benchtop
characterization were performed and investigated.
TCR and OHTexperiments allowed us to predict the temperature of the heater and determine
the appropriate current to apply to open the valve. Opening powers of 25-50
mW were obtained. Further work will be done to reduce power consumption.
Also, additional experiments will evaluate the performance of the valve in thepresence of drug and in vivo. In addition, this Parylene C electrothermalvalve will be integrated into a reconfigurable microfluidic device.
Acknowledgements. This work was funded in part by the NIBIB (1R01 NS050171). The authors would like to thank Dr. Tina K. Givrad, 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 5. Images showing (a) an open valve after 15 mA applied current and(b) magnified view of the edge of the valve orifice.

Polymer Preprints 2008, 49(1), 942