Biomed Microdevices (2013) 15:37–48
DOI 10.1007/s10544-012-9685-0

A MEMS electrochemical bellows actuator for fluid
metering applications
Roya Sheybani & Heidi Gensler & Ellis Meng

Published online: 26 July 2012
# Springer Science+Business Media, LLC 2012

Abstract We present a high efficiency wireless MEMS electrochemical bellows actuator capable of rapid and repeatabledelivery of boluses for fluid metering and drug delivery applications. Nafion®-coated Pt electrodes were combined with
Parylene bellows filled with DI water to form theelectrolysis-based actuator. The performance of actuators withseveral bellows configurations was compared for a range ofapplied currents (1–10 mA). Up to 75 boluses were delivered
with an average pumping flow rate of 114.40±1.63 μL/min.
Recombination of gases into water, an important factor in
repeatable and reliable actuation, was studied for uncoatedand Nafion®-coated actuators. Real-time pressure measurements were conducted and the effects of temperature, physiological back pressure, and drug viscosity on delivery
performance were investigated. Lastly, we present wirelesspowering of the actuator using a class D inductive poweringsystem that allowed for repeatable delivery with less than 2 %variation in flow rate values.

Keywords MEMS electrochemical bellows actuators .
Wireless powering . Fluid metering . Patient tailoredsite-specific drug delivery devices

R. Sheybani : H. Gensler : E. Meng
Department of Biomedical Engineering,
Viterbi School of Engineering, University of Southern California,
1042 Downey Way, DRB-140,
Los Angeles, CA 90089-1111, USA
E. Meng (*)
Department of Electrical Engineering,
Viterbi School of Engineering, University of Southern California,
3651 Watt Way, VHE-602,
Los Angeles, CA 90089-0241, USAe-mail: ellis.meng@usc.edu

1 Introduction
Drug delivery is essential in the treatment and managementof chronic conditions such as hypertension, respiratory disease, and diabetes that plague some 125 million Americans(Menehan 2006). However, the most commonly used administration routes, oral or injection, require high systemic
doses to achieve the intended therapeutic effect at a remotetargeted site within the body. The collateral damage that
results from adverse reactions to such high doses motivate
the desire to develop implantable site-specific drug delivery
systems that minimize side effects, improve safety, and havethe potential to be more effective by allowing the use of
more potent drugs (Fiering, Mescher et al. 2009). Over thelast two decades, microelectromechanical systems (MEMS)
micropumps have been developed for broad biomedical andbiological applications (Laser and Santiago 2004). A subsetof these pumps address requirements for implantable drugdelivery systems including biocompatibility, reliable operation (precise and accurate flow control), low power consumption, low heat generation, large driving force, andcompatibility with a large variety of new and conventional
drugs (Geipel, Goldschmidtb et al. 2008; Tang, Smith et al.
2008; Amirouche, Yu et al. 2009). However, the emphasis
has been on continuous pumping. New evidence in chronotherapy studies point to the therapeutic benefits of the timely
delivery of drug, both in terms of duration and time point,
within the targeted tissue’s therapeutic window (Bruguerolleand Labrecque 2007). Thus, it is clinically relevant to investigate MEMS-based implantable drug delivery technologies that can provide controlled drug volumes at specifictimes and locations within the body.
Timing and precision of delivery of liquid formulations
depend on pump microactuator performance. Thus, selection of actuation methods, dynamic or displacement, aredictated by performance requirements relating to parameters38such as flow rate, back pressure, power, efficiency, reliability, and size (Laser and Santiago 2004; Nguyen and Wereley2006). Dynamic micropumps continuously add energy to
the working fluid by directly increasing pressure or momentum; in the latter, conversion into pressure is achieved
through an external fluid resistance. Among dynamic actuation methods, magnetohydrodynamic (MHD-DC) actuators are capable of delivering flow rates of up to 1200
μL/min (Bruguerolle and Labrecque 2007), however, theworking fluid must be conductive and the system requires
external electric and magnetic fields (Tsai and Sue 2007)
that increase power, size, and cost. Displacement micropumps, on the other hand, exert pressure forces on theworking fluid using one or more moving boundaries (Laserand Santiago 2004). Electrostatic (Judy, Tamagawa et al.
1991) and piezoelectric (Junwu, Yang et al. 2005) actuators
in displacement micropumps are capable of delivering highflow rates (>50 μL/min), and yet are generally larger in size,
structurally complex, and require high power (Tsai and Sue2007). Such actuator types are generally not suitable ordifficult to implement in vivo.
Electrochemical actuation offers many advantages fordisplacement micropumps, including large driving force,
accurate flow control, low power consumption, and low
heat generation (Li, Sheybani et al. 2010). The large volume
expansion achieved by electrolysis of water to form oxygenand hydrogen gas can be harnessed for actuation (Tsai and
Sue 2007). Current control of electrolysis allows for ondemand activation of delivery and selection of flow rate;
the current magnitude and resulting flow rate are linearlycorrelated for flow control over a wide range of flow rates.
Dose volume is selected by pump activation time for aparticular flow rate which enables intermittent drug delivery.
Electrochemical pumps could have biocompatible construction and wireless actuation (Li, Sheybani et al. 2010) and are
well suited for in vivo drug delivery applications. In addition, the metering capability of such pumps is also useful for
microfluidics and lab-on-a-chip applications.
Previously, we reported evaluation of Nafion®-coatedelectrodes for continuous electrolysis-based pumping; coating significantly improved the repeatability and efficiency
of current-controlled electrolysis (Sheybani and Meng2012). Using electrode-only actuators, reliable, precise,and accurate flow control with low power consumption,
low heat generation, and large driving force was demonstrated. Here, we present the design, fabrication, and characterization of electrochemical bellows actuators having
Nafion®-coated electrodes for controlled intermittent pumping of fluid boluses. Such capability is motivated by unmet
needs in chronic drug delivery applications (Fig. 1). The
Parylene bellows separates the electrolysis reaction from thepumped drug to prevent unwanted electrochemical or chemical interactions. Electrolysis gases are trapped within the

Biomed Microdevices (2013) 15:37–48

Fig. 1 Illustration of operation concept of electrochemical bellows
actuator. Actuator is shown housed within a reservoir to illustrate thecase of fluid metering through an attached catheter

bellows preventing their delivery with the fluid. A new highyield process produced robust bellows consisting of arbitrary numbers of convolutions which were capable of withstanding higher pressures and cycling encountered in highflow rate, rapid bolus delivery (Gensler, Sheybani et al.
2011).
Characterization of actuator flow performance is presented,
including characterization during recombination phase(current off) with and without the addition of a commercial
check valve. Real-time pressure measurements for an actuatorwith a 2 convolution bellows, as well as, the influence ofchanges in temperature, drug viscosity, and applied backpressure on flow rate and delivery accuracy, are discussed. Finally, a wireless powering system and wirelessoperation results are described.

2 Theory
Water electrolysis is initiated when a sufficient potential or
current is applied to a pair of electrodes in contact with anelectrolyte (water). The reaction induces water dissociation
into oxygen and hydrogen gas. At the anode, oxygen gas,
protons, and electrons are produced. The protons are thendriven through the electrolyte to the cathode and combinewith electrons in the external circuit to form hydrogen gas at
twice the rate of oxygen (Bohm, Timmer et al. 2000). A 3:2
stoichiometric ratio conversion of gas to liquid with theBiomed Microdevices (2013) 15:37–48

39

standard potential (E° (25 °C)) of -1.23 V results (Cameronand Freund 2002; Choi, Bessarabov et al. 2004). The reactions at each electrode and the net reaction are summarizedin Eqs. 1, 2 and 3. The theoretical achievable volume
expansion from liquid water to gas phase hydrogen at room
temperature is 136,000 % (Cameron and Freund 2002). Thislarge volume change proceeds even in a pressurized environment making electrolysis an attractive actuation method(Li, Sheybani et al. 2010).
At anode :At cathode :H2 OðlÞ!2H þ ðaqÞ þ 2e þ 0:502 ðgÞ
2H þ ðaqÞ þ 2e !H2 ðgÞ

Net reaction : H2 OðlÞ!H2 ðgÞ þ 0:502 ðgÞ

ð1Þ
ð2Þ
ð3Þ

A number of molecular processes influence the rate ofgas evolution and the performance of electrolysis actuators.
Electrolytically evolved gas first dissolves in the electrolyte
adjacent to the electrodes leading to supersaturation of theadjacent electrolyte facilitated by the low solubility andsmall diffusion coefficient of oxygen and hydrogen gases
in water. At low current densities, the dissolved gas remains
in the electrolyte (Bohm, Timmer et al. 2000) and is transported to the surrounding bulk electrolyte solely throughdiffusion, and so supersaturation near the electrodes
becomes constant. However, at higher current densities,
supersaturation will exceed the threshold required for bubble formation. Bubbles form on the electrode and detachonce the Archimedes’ force on the bubble exceeds surface
adhesion forces (Verhaart, De Jonge et al. 1980; Neagu
1998). Mass transfer of gases controls bubble growth(Shibata 1978) and under constant current conditions, is
proportional to the square root of time (Sillen, Barendrecht
et al. 1982). Thus, constant current is the preferred mode forelectrolysis actuation.
There are no side reactions that could produce undesirable products and potentially reduce the efficiency of gas
generation (Neagu, Jansen et al. 2000; Xie, Miao et al.
2004). Gas generation efficiency may be reduced by dissolution of gases into the solution, recombination of gases into
water, Joule heating, pressure drop across the actuator
membrane, and diffusion of gases through the membrane(Stanczyk, Ilic et al. 2000; Xie, Miao et al. 2004). Efficiency
can be improved by increasing current density throughmethods such as increasing electrochemically active electrodesurface area and minimizing occlusion by evolved gases orgas films (Neagu, Jansen et al. 2000).
Over time, the slow diffusion of oxygen through water
results in the formation of an “O2 film” on the electrodesurface (Shibata 1978). This film impedes further electrolysis
by preventing liquid-metal contact (Sillen, Barendrecht et al.

1982). Nafion®, a solid polymer electrolyte manufactured by
Dupont, was introduced in (Sheybani and Meng 2012) toimprove efficiency. Solubility of O2 and H2 is 1.8 times higher
in Nafion® compared to water (Maruyama, Inaba et al. 1998).
This allows for rapid diffusion of gas bubbles away from thesurface of the electrodes and prevents occlusion by the gas
film. It was reported that Nafion® coated electrodes exhibiteda 20 % increase in current density (Maruyama, Inaba et al.
1998).
Once the current is removed, gases recombine to form water,
however, this reaction is limited by high overpotentials andhigh activation energy (Broka and Ekdunge 1997; Gensler,
Sheybani et al. 2012). Pt can catalyze recombination and isthus commonly selected as the actuator electrode material. In
this case, recombination rate is subject to the slow diffusion ofO2 and H2 to the surface of the Pt electrodes.

3 Actuator operation, design, and fabrication
The bellows actuator consists of an electrolyte-filled chamber formed by a Parylene bellows and rigid substrate supporting a pair of interdigitated Pt/Ti electrodes. For pumping
applications such as drug delivery, the bellows is coupled toa fluid reservoir. Current application induces electrolysis
and the volume expansion inflates the Parylene bellows
which expels fluid in the reservoir through an outlet catheter(Fig. 1). Recombination of the gases to water when thecurrent is turned off allows the bellows to return to theoriginal starting position ensuring reliable actuator operationand preventing irreversible damage to the bellows.
A bellows was selected over a corrugated or flat diaphragmfor its greater achievable deflections at lower applied pressures (Li, Sheybani et al. 2010). Moreover, additional convolutions are easily added to increase achievable deflection
without significantly increasing overall device size (Gensler,
Sheybani et al. 2011). Parylene bellows (1, 1.5, and 2 convolutions; 9 mm outer diameter, 6 mm inner diameter) were
fabricated as described in (Gensler, Sheybani et al. 2011) andusing a new process compared to (Li, Sheybani et al. 2010)(Figs. 2–3). Briefly, 0.4 mm thick silicone rubber sheets (10:1
base-to-curing agent ratio Sylgard 184, Dow Corning, Midland, MI) were punched with 9 and 6 mm holes, aligned, andstacked in alternating layers on glass slides as to form moldmodules. These molds were filled with molten (~50 °C)
polyethylene glycol (PEG; 1,000 Mn, Sigma Aldrich, St.
Louis, MO), taking care to ensure that no air bubbles wereintroduced to the molds. Once PEG solidified at room temperature, silicone molds were peeled away to release the solid
PEG modules. The modules were stacked and fused together
by slightly moistening interfaces with water. A 13.5 μm layerof Parylene C (Specialty Coatings Systems, Indianapolis, IN)
was deposited over the PEG mold, and PEG was dissolved by40

Biomed Microdevices (2013) 15:37–48

Fig. 2 Illustration detailing theelectrode and bellows
fabrication processes andbellows actuator assembly.
A 2 convolution bellows
is shownsoaking in water at room temperature to complete the bellows.
The number of convolutions were chosen based on previous
deflection data (Li, Sheybani et al. 2010; Gensler, Sheybani etal. 2011) and kept low to minimize the overall actuator height.
Interdigitated Pt electrodes (100 μm wide elements separated by 100 μm gaps, 8 mm diameter footprint, 300 Å/2000 Å
Ti/Pt) were fabricated on soda lime substrates by liftoff following e-beam deposition of the thin film metal using a previous
developed process (Figs. 2–3) (Gensler, Sheybani et al. 2012;
Sheybani and Meng 2012). The electrode layout was selected
to maximize electrolysis reaction efficiency (Li, Sheybani et al.
2010). Electrodes were potentiostatically cleaned at ±0.5 V(Gamry Reference 600 Potentiostat, Warminster, PA) in 1X
phosphate buffered saline. To produce a 1 μm thick coating,Nafion® (Dupont DE521Solution, Ion Power, INC, New Castle, DE) was applied by dip coating twice. Conductive epoxy(Epo-tek® H20E, Epoxy Technology, Billerica, MA) was used
to affix Kynar™ silver plated copper wires (30 AWG, Jameco
Electronics, Belmont, CA) to contact pads on the electrodes.
The joint was strengthened and insulated with nonconductive
marine epoxy (Loctite, Westlake, OH) (Sheybani and Meng2012).
To assemble the actuators, bellows were cut to size using arazor blade, filled with DI water, and carefully combined with
Fig. 3 Photograph of: (a)Pt electrolysis electrode, (b) 2
convolution Parylene bellows,(c) assembled bellows actuator

the Nafion®-coated interdigitated Pt electrodes using laser cut
double-sided pressure sensitive adhesive film (3M™ Double
Coated Tape 415, 3M, St. Paul, MN). The seal was reinforced
with marine epoxy (Loctite, Westlake, OH; Figs. 2–3).

4 Experimental methods
The performance of actuators was systematically characterized. First, actuator performance under continuous pumping
conditions at different currents and for each of the three different bellows configurations (1, 1.5, and 2 convolutions) wasinvestigated. The pressure increase during pumping mode was
acquired in real time. Recombination mode operation with orwithout a commercial check valve at the outlet to prevent
backflow of fluid during the recombination phase was investigated. Then bolus delivery was assessed for several delivery
regimens in which flow rates, bolus volumes, and number ofboluses were varied. The study of rapid and repeated bolus
mode operation is driven by the potential application of selfadministration drug addiction studies in small animals. In thisparadigm, doses must be administered immediately (< 5 s) andrepeatedly in response to designated activities to allow the
study of correlations between behavior and drug addiction.

Biomed Microdevices (2013) 15:37–48

The impact of environmental factors and fluid composition on
pumping were investigated by varying temperature, appliedback pressure, and viscosity. Finally, wireless operation of theactuator was demonstrated.
4.1 Pumping mode actuator characterization
under continuous operation
The flow rate performance of each bellows configuration
under continuous operation was assessed by clamping theactuator within a reservoir formed by an acrylic test fixture
filled with double distilled water. Constant current was
supplied to the electrolysis electrodes for 2 min (Keithley
2400, Keithley Instruments Inc., Cleveland, OH). Flow rate
was calculated using the weight of accumulated pumped
water. All other experiments were performed with bellows
having 2 convolutions to maximize the fluid volume accessible by the actuator for electrolysis.
Real-time measurements of electrolysis chamber pressure
were collected at different currents (1, 2, 5, 8, and 10 mA)
using a pressure sensor (ASDX015D44R, Honeywell International Inc., Morristown, NJ) connected directly to theoutlet of the test fixture. Sensor data was sampled using adata acquisition unit (LabVIEW 9.0.1 with NI cDAQ-9174,
National Instruments Corp., Austin, TX). Each current wasapplied for 90 s during which the pressure was measured inreal-time.
4.2 Recombination
In order to fully investigate the recombination behavior of theactuator, a large range of volumes of generated gases wererequired, some of which were beyond the bellows operating
range. Therefore, recombination experiments were performed
without the Parylene bellows.
Flow rate performance of uncoated and coated electrodes
was acquired within an acrylic test fixture filled with double
distilled water. The same test fixture was used for all experiments in order to keep the volume of the electrolysis chamber
constant. The generated and recombined gas volumes were
calculated by measuring water front displacement in a calibrated
100 μL micropipette attached to the test fixture outlet. Different
volumes of gas were generated by varying the duration of
10 mA current application. ON/OFF times were equal. Anotherset of experiments were carried out, in which the volume of gas
generated was varied by applying different constant current
values (1, 2, 5, 8 mA) for 2 min. Recombination was observed
for an hour following each current application.
4.3 Bolus delivery
Actuator performance mimicking conditions necessary for
drug self-administration was investigated in three studies.

41

Bolus delivery and recombination were compared in uncoated and Nafion®-coated bellows actuators for rapid-fire delivery of groups of 3 boluses at 10 mA (15 s ON, 10 s OFF)separated by 5 min OFF cycles. Forty boluses were delivered at 10 mA (15 s ON, 60 s OFF). Seventy-five boluses
were delivered at 10 mA (2 s ON, 60 s OFF) using a bellows
having a larger outer diameter (10 mm).
While recombination is essential to reliable actuation, it
also results in a reverse pressure gradient. Backflow into thepump was prevented by connecting a commercial check valve
between the reservoir and the outlet catheter. A Qosina 80031
in-line check-valve with < 0.35 kPa (0.05 psi) cracking
pressure, acrylic and ethylene propylene diene monomer construction, and a 3.1–3.43 mm outer diameter (Qosina, Edgewood, NY) was selected. 15 boluses were delivered at 10 mA(15 s ON, 60 s OFF). Accumulated volume was calculated bymeasuring water displacement in a 100 μL calibrated
micropipette.
4.4 Flow performance at body temperature
Broka et al. (Broka and Ekdunge 1997) showed that permeability of Nafion® to oxygen and hydrogen increased slightly
when ambient temperature was raised from room (25 °C) tobody temperature (37 °C). Increased permeability of Nafion®
may lead to increased reaction rates and more effective pumping. Temperature effects on flow performance were evaluatedusing a Nafion®-coated electrode (without bellows) in an
acrylic test fixture placed in a constant temperature water bath.
Flow rate was calculated by weighing pumped water accumulated over 2 min of current application. Then, rapid-fire delivery of 10 boluses at 8 mA (5 s ON, 1 min OFF) at room (25±0.2º C) and body temperatures (37±0.2º C) were performed
on a Nafion®-coated actuator with a 2 convolution bellows.
Accumulated volume was calculated by measuring water
displacement in 100 μL micropipette.
4.5 Pumping of viscous fluids
The effects of viscosity on flow performance were investigated using three different model drug solutions (propylene glycol, diluted ISOVUE 370, and cocaine). Propylene glycol is acolorless and odorless alcohol compound that has been used
as a solvent and a drug carrier in pharmaceutical products(Ooya and Yui 2000; Kogan and Garti 2006; Lee, Oh et al.
2010). ISOVUE 370 is a contrast agent containing iodine usedin radiological examinations. Cocaine is a suitable agent forstudying drug addiction in a self-administration paradigm insmall animals. For propylene glycol, several concentrations
were prepared by diluting stock with DI water. ISOVUE 370(Bracco Diagnostic Inc., Princeton, NJ) was diluted 1:1 with
DI water. Cocaine was dissolved in 0.9 N saline. The viscosityof these solutions was measured using a Cannon-Fenske

42routine viscometer (Technical Glass Products, PainesvilleTwp., OH) immersed in a water bath at 37 °C.
Model drug solutions were loaded into a polypropylene
reservoir containing a Nafion®-coated, 2 convolution bellows actuator. Multiple boluses were delivered (propylene
glycol: 10 boluses at 8 mA (10 s ON, 60 s OFF); ISOVUE
370: 3 boluses at 3 mA (90 s ON, 30 min OFF); cocaine 3boluses at 8 mA (60 s ON, 15 min OFF)) and the flow rate wascalculated from measuring fluid displacement in a 100 μL
calibrated micropipette or by weighing the accumulated
dispensed fluid.
4.6 Effects of applied back pressure on flow performance
During in vivo pumping, the actuator must overcome any backpressure associated with the local physiological conditions near
the catheter outlet. For instance if the drug is to be delivered in
the thoracic vena cava, the backpressure would be equal to thecentral venous pressure (CVP). The normal range in humans
was reported to be approximately ~ 3–8 mmHg (Goers 2008).
A range of back pressures close to the CVP were applied inorder to study their impact on bolus delivery. Four boluses weredelivered at 5 mA (60 s ON, 120 s OFF).
4.7 Wireless powering system
A 2 MHz class D wireless powering system was developed for
wireless operation (Sheybani and Meng 2011) (Fig. 4). Wireless power transfer was performed with concentric placementof the primary (Ø 55 mm) and secondary (Ø 23 mm) coils andin the same plane (0º foveation between coils). Twenty boluses
were delivered at 6.3 mA (5 s ON, 60 s OFF) using an actuatorhoused in a polypropylene reservoir with 1 mL volume.

5 Experimental results
5.1 Pumping mode actuator characterization
under continuous operation
Flow rate is linearly dependent on applied current (Sheybani
and Meng 2012). The addition of the drug separating bellows
Fig. 4 Circuit schematic forclass D wireless inductive
powering system

Biomed Microdevices (2013) 15:37–48

does not affect this relationship. As expected, flow rates werecomparable for bellows with different convolutions (Table 1)
and not significantly different as confirmed by statistical analysis of the obtained flow rates (ANOVA, p<0.05). The 1
convolution bellows, however, was expanded beyond its elastic
operation range at 10 mA current and irreversibly damaged.
Actuator operating range is therefore limited by the mechanicalperformance of the bellows selected.
Nafion® coating increased electrolysis efficiency leading
to faster pressure buildup and subsequently higher flow
rates. Figure 5 shows the results for real-time pressure
measurement of actuators having coated electrodes for different applied current values. As expected from the flow
characterization results, the slope was linearly dependent on
the applied current (R2 00.9976). Slope can be used to estimate pressure generated at a particular instant in time for agiven applied current.
5.2 Recombination
Oxygen reduction (recombination) requires a Pt catalyst. For
uncoated electrodes, recombination proceeds slowly as it islimited by slow diffusion of gases through water towards thesurface of the Pt catalyst (Neagu 1998). Oxygen and hydrogengases have a higher solubility in Nafion® compared towater (Maruyama, Inaba et al. 1998) (O2 solubility is 7.2×
10−6 mol.cm−3 in hydrated Nafion® (Ogumi, Takehara et al.
1984) and H2 solubility is 1.4×10−6 mol.cm−3 in hydrated
Nafion® and 0.78×10−6 mol.cm−3 in water (Maruyama, Inabaet al. 1998)). The higher solubility facilitates diffusion of gases
to the electrode surface and may also establish a concentration
gradient that further drives diffusion; therefore, recombination
is facilitated and increased in Nafion®-coated compared touncoated electrodes (Fig. 6). When the Parylene bellows are
combined with Nafion®-coated electrodes, recombination follows a predictable non-linear diffusion dependent pattern and99.08 % recombination is achieved within 1 hour of delivery(145 μL delivered volume, data not shown). As expected fromthe recombination results for electrodes only, gas bubble
interactions on the surface of uncoated electrodes and slow
diffusion of gases through water, lead to a random and unpredictable recombination rate. With Nafion® coating, direct

Biomed Microdevices (2013) 15:37–48

43

Table 1 Flow rate values for 1, 1.5, and 2 convolutions bellows
actuators, n=3, Mean±SE (Sheybani, Gensler et al. 2011a, b)
Current [mA]

1
2
5
8
10

Flow Rate [μL/min]
1 Convolution

1.5 Convolution

2 Convolution

7.33±0.17
17±0.2944.33±2.42
75.5±1.80
N/A

9.88±0.31
19.54±0.54
49.05±3.05
72.44±5.35
100.61±1.11

7.04±0.29
17.33±0.4448.17±0.33
73.66±0.4487.33±0.83

bubble interaction with electrodes is avoided. Recombination
rate is a function of three factors, transport of gas throughwater to Nafion®, transport of gas through Nafion® to theelectrode, as well as, ratio of gas to liquid inside the bellows.
For Nafion®-coated electrodes, recombination is not directly dependent on applied current or its duration. Rather, it
is dependent on the volume of gas generated during theactuation phase. Gas recombination occurs in two phases.
The rate is diffusion limited while bubbles are diffusing
through the water and Nafion® to the surface of the catalyst
but once a sufficient volume of gas bubbles are available at thesurface of the catalyst, the recombination becomes reaction
limited (Verheij 1997). It is important to note that recombination is also dependent on the volume of the vessel in whichelectrolysis occurs. The smaller the volume, the shorter thepath the gas bubbles need to diffuse to reach the surface of theelectrode which facilitates recombination.
5.3 Bolus delivery
When comparing bolus delivery results between coated anduncoated electrodes, differences in both delivery rate as well
as recombination are readily observed: the overall pumping
efficiency under identical operation conditions is increased
and recombination rate is highly dependent on gas to liquidratio (Fig. 7). An average flow rate of 78.98±1.68 μL/min(mean ± SE) was calculated for the 40 boluses delivered. As
evident in Fig. 8, the transition from diffusion limited toFig. 5 (a) Real-time pressure
measurements of a 2 convolution Nafion®-coated bellows
actuator under constant current
application; (b) Slope values forreal-time pressure vs. time fordifferent current values

reaction limited regimes of recombination occurred after ~175 μL of accumulated volume was delivered and limited
further delivery. 75 boluses (3.81±0.05 μL (mean ± SE) per
bolus) were delivered using the Parylene bellows with thelarger outer diameter (10 mm) (Fig. 9). The aforementioned
recombination regimes are dependent on the size of thebellows and its remaining water content. The transition between the two regimes occurs when a particular gas to liquidratio threshold is reached. As expected based on previous
studies detailed in (Gensler, Sheybani et al. 2011), the bellows
having larger diameter achieved higher expansion, therefore,
the change in regime would occur at larger volumes that are
not reached in Fig. 9.
With the bellows actuator connected to the commercial
check valve, 15 boluses were delivered with an averagebolus volume of 26.22±0.18 μL per bolus (mean ± SE).
The cracking pressure of the commercial check valve wasreported by the manufacturer to be 0.345 kPa (0.05 psi,
2.6 mmHg). Figure 10 shows that this cracking pressure
was adequately exceeded by the actuator. The valve did
not increase response time or impede flow compared towhen the actuator was operated without a valve. These
results correspond to the aforementioned real-time pressure
measurements for the bellows actuator. However, as previously reported in (Gensler, Sheybani et al. 2012), this valve
is not normally-closed as advertised and requires a finite
back pressure for complete sealing. This sealing pressure(measured to be greater than 1.03 kPa) against backward
flow was not reached under this condition, leading to significant leakage after the delivery session. It is important tonote, that backflow can be prevented with a true normallyclosed check valve.
5.4 Flow performance at body temperature
Flow rate calculations are summarized in the table below(mean ± SE, n03) for continuous pumping with Nafion®coated electrode only actuators at room and body temperature (without bellows). A slight increase in flow rate wasapparent at 37 °C as expected (Table 2).

44

Biomed Microdevices (2013) 15:37–48

Fig. 6 Comparison between
recombined volume for uncoatedand coated electrodes: (a) current
controlled (10 mA) delivery for
different ON/OFF times(Sheybani, Gensler et al. 2011)
and (b) time controlled (2 min)flow rate delivery at different
applied currents

The slight increase in flow rate was also observed for rapidfire boluses delivered using actuators with a 2 convolution
bellows. 10 boluses with an average volume of 15.47±
0.13 μL and 16.33±0.18 μL per bolus (mean ± SE) weredelivered at room (25 °C) and body temperature (37 °C),
respectively. The flow rate differences were significant as
determined by t-test for two independent samples with unequal variances (p<0.01).
5.5 Pumping of viscous fluids
Despite the large range of viscosities, change in propylene
glycol solution flow rate was less than 2.4 % (Fig. 11). One
way analysis of variance of the data showed that the changes
in flow rate for different viscosities were not significantly
different compared to one another (p<0.05). Similarly for
the ISOVUE 370 dye, an average flow rate of 30.00 ±0.0 μL/min was measured compared to 29.33±0.0 μL/min
for water (mean ± SE). The dye solution was not viscousenough to impede pumping. However, the effects of drug

Fig. 7 Comparison between rapid-fire bolus delivery using uncoatedand coated 2 convolution bellows actuators (3 boluses at 10 mA, 15 s
ON/10 s OFF, separated by 5 min OFF cycles (Sheybani, Gensler et al.
2011))

concentration (effectively viscosity) were more apparent inhigh concentrations of cocaine and flow rate decreased 21 %for 25.73 mg/mL cocaine solution (Fig. 12, viscosity could
not be measured due to limited sample).
5.6 Effects of applied back pressure on flow performance
The change in flow rate across the range of relevant physiological back pressures was less than 5.5 % (Fig. 13). One way
analysis of variance of the data demonstrated that changes inflow rate across the different back pressure were not significantly different compared to one another (p<0.05).
5.7 Wireless powering system
Data for wirelessly operated actuators is summarized inTable 3 (Sheybani and Meng 2011). The standard error
calculated for different runs at the same set current
value was less than 2 % which is less than whenpowered using the constant current source. The averageFig. 8 Bolus delivery with a Nafion® coated, 2 convolution bellows
actuator (at 10 mA current, 15 s/1 min ON/OFF, modified from (Sheybani,
Gensler et al. 2011))

Biomed Microdevices (2013) 15:37–48

45
Table 2 Flow rate values for current controlled delivery at room
temperature vs. body temperature
Current [mA]1
2
58

Fig. 9 Bolus delivery with a Nafion® coated, 2 convolution bellows
actuator (at 10 mA current, 2 s/1 min ON/OFF), inset: close-up for first
10 boluses delivered

flow rate calculated for the 20 boluses delivered was 68.4±
1.23 μL/min (mean ± SE).

6 Discussion
An electrochemical actuator specified for insulin delivery wasreported by Suzuki and Kabata in 2005. The system usedhydrogen production to deflect a flat silicone membrane tocause actuation and achieved a flow rate of 13.8 μL/min(Kabata, Suzuki et al. 2005). However, with this system, repeatable and reliable delivery could not be achieved since the
Ag/AgCl electrode depleted over time so that actuator performance was not consistent. Also, the flat silicone membrane had
limited deflection and could potentially leak, allowing toxic
Ag+ in the body. We previously reported an electrochemical
bellows actuator capable of delivering flow rates up to 6.5 μL/
Fig. 10 Bolus delivery using
an actuator with an in-line
check valve (at 10 mA current,
15 s ON/60 s OFF). After 15boluses, the actuator is turned
off. Inset shows average accumulated volume for 15 boluses

Flow Rate @25±0.2 °C [μL/min]

Flow Rate @37±0.2 °C [μL/min]

8.89±0.68
21.33±0.61
54.44±1.84
89.89±0.78

11.56±0.47
21.47±0.50
53.7±2.96
94.44±1.15min (at 1 mA) but with uncoated electrodes (Li, Sheybani et al.
2010). The pumping efficiency was significantly increased by
Nafion® coating of the Pt electrodes (94 % for 13 mA compared to 53 % for uncoated electrodes) and reliable andrepeatable delivery was achieved (Sheybani and Meng2012). A new high yield process produced robust bellows
consisting of arbitrary numbers of convolutions which werecapable of withstanding higher pressures and cycling encountered in high flow rate, rapid bolus delivery (Gensler, Sheybani et al. 2011).
The different bellows configurations did not affect the flow
rate, however, increasing the number of convolutions increased
accessible fluid volume for actuation (Gensler, Sheybani et al.
2011). For the 1 convolution bellows, the electrolyte volumecontained is less, therefore as the water to gas ratio becomes
smaller, less water is available for further electrolysis. This
could lead to increased power consumption (reaching up to
120 mW for 10 mA applied current for the 1 convolution
bellows after 1.67 min of actuation).
Recombination, catalyzed by the Pt electrodes when thecurrent is turned off, is an important factor for reliable andrepeatable delivery. Nafion®-coated electrodes resulted in a
faster and more predictable pattern of recombination which
can in turn be used to tune delivery parameters applied to the46

Biomed Microdevices (2013) 15:37–48

Fig. 13 Flow delivery results for a range of physiologically relevantback pressures (at 5 mA constant current)

Fig. 11 Flow delivery results for of different viscosities of propylene
glycol (at 8 mA constant current)

actuator to achieve repeatable and reliable delivery andensure the bellows are not driven beyond their elastic limit.
A truly normally closed check valve is required to prevent backflow of fluids as a result of the reverse pressure
gradient caused by recombination. Alternatively, a pressurecompensation chamber could be utilized to remedy suchcomplications.
Various environmental factors such as temperature, fluid
viscosity, and back pressure could affect actuation flow rateand efficiency. For each application, the environmental factors

should be carefully evaluated. Changing the actuation temperature from room temperature (25 °C) to body temperature(37 °C) showed to cause a significant rise in flow rate; this
could be attributed to the slight increase in permeability of
Nafion® to oxygen and hydrogen when ambient temperatureis raised from room (25 °C) to body temperature (37 °C)(Broka and Ekdunge 1997). The actuator is able to pump fluid
over a wide range of viscosities, however, for sufficiently highviscosities (> 26 cSt), the flow rate may be affected. A range
of applied back pressures within the normal range of CVP in
humans (approximately ~ 3–8 mmHg (Goers 2008)) did notaffect the actuation flow rate significantly.

7 Conclusion
We demonstrated the design, fabrication and characterizationof a high efficiency electrochemical bellows actuator capableof rapid and repeatable bolus delivery (up to 75 bolusesdelivered with an average pumping flow rate of 114.40±
1.63 μL/min in less than 78 min) with low power consumption in the mW range (2–25 mW for 1–10 mA applied current). Real-time pressure measurements of the actuatorconfirm the linear relationship observed between applied current and flow rate. Recombination, essential to accurate andTable 3 Flow rate values for current supplied
using the wirelesspowering system

Fig. 12 Current controlled flow delivery of cocaine (in 0.9 N saline)
loaded in a pump at different concentrations (at 8 mA, 1.5 convolution
bellows, modified from (Sheybani, Gensler et al. 2011a, b))

Current
[mA]
2
5
8
10

Flow Rate with Wireless
System [μL/min]
20.00±0.14
59.00±1.11
98.67±0.41
125.67±1.44

Biomed Microdevices (2013) 15:37–48

repeatable delivery was studied and it was shown that a
predictable pattern can be discerned for Nafion®-coated electrodes. Effects of body temperature, physiological back pressure, and drug viscosity on delivery performance were
investigated. Lastly, we presented wireless powering of theactuator using a class D inductive powering system thatallowed for repeatable delivery with less than 2 % variationin flow rate values. Future work includes, improving wirelesssystem to reduce power requirements and heat dissipation,
designing a more suitable check-valve to completely prevent
backflow of fluid towards the actuator, and fully packaging
the actuator inside a rigid biocompatible polypropylene drug
reservoir.

Acknowledgments This work was funded in part by a Wallace H.
Coulter Foundation Early Career Translational Research Award and
NIH/NIDA under award number R21DA026970. The authors would
like to thank Ms. M. Wong for providing the ISOVUE 370 solution,
Drs. D. Holschneider, J.M. Maarek, D. Zhu, and the members of the
USC Biomedical Microsystems Laboratory for their assistance withthis project.

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