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Ex Vivo Monitoring of Rat Heart Wall Motion
Using Piezoelectric Cantilevers
Rui Zhang1, Ya Chen2, Wen H. Ko1, David S. Rosenbaum3,4, Xin Yu2,3, Philip X.-L. Feng1
1Electrical Engineering, 2Biomedical Engineering, Case School of Engineering3Physiology and Biophysics, Case School of Medicine, 4MetroHealth System
Case Western Reserve University, Cleveland, OH 44106, USACorresponding Authors; Email philip.feng@case.edu, xin.yu@case.edu
Abstract We report on an experimental exploration ofex vivo
measurements and real-time monitoring of the motions of heart
wall for perfused rat hearts, by employing a surface-contact type
of electromechanical probes based on piezoelectric transduction.
In a hybrid experimental apparatus consisting of a conventional
heart perfusion system and external electromechanical probing
devices and circuitry, prototyped piezoelectric cantilever devices
are calibrated and tested. We demonstrate that the externalpiezoelectric cantilevers are capable of monitoring the dynamic
behavior of the isolated heart ex vivo, by measuring the motions
of the heart wall. For typical rat hearts with heart rates in the
range of ~150250bpm (beats per minute), cantilevers with
dimensions of t wL | 130m (0.38)mm (119)mm yield
electrical signal of ~50400mV. Measured data can also helpidentify signatures of various regimes (e.g., from healthy to
fatigued, to expiring) in the dynamical evolution during the
perfused hearts lifetime. Preliminary tests on parallel multi-
channel monitoring with probes positioned at multiple locations
on heart surface prove to be valid and useful in obtaining
information of regional displacement of heart wall.
I. INTRODUCTIONHeart is the foundation of advanced lives including human
being. Heart health and function monitoring are critical,
especially for patients who suffer from heart diseases. Heart
diseases are the top one cause of death in the United States
and several other countries (e.g., a total death of ~600,000 per
year in 20072009 in US means one death due to heart disease
every ~50 seconds) [1], and are the top reason for disease-
based deaths throughout the world. This drives researchers to
push the limits in advancing heart healthcare technology. We
perceive at least the following major challenges (i) early
detection of alarms of heart diseases for apparently healthypeople it is desirable to develop devices that are wearable or
implanted (with very low pain), especially for old people,athletes, and those who may have family history of heart
diseases; (ii) post-surgery chronic heart monitoring for
patients who are already receiving surgery and other treatment
what is desired includes low-pain implantable solutions that
are small, light, enduring, and compatible with telemetry.
To date it has been well recognized that regional strain and
stress on heart wall are related to development of disease [2],
and studying the electromechanical properties and monitoring
heart wall motion can help for heart diseases diagnosis [3].
From an engineering perspective, the heart is an amazing
electromechanical device with exquisitely elegant functions
and structures (Figure 1) enabled by soft materials and tissues
this causes some of the fundamental issues that are
challenging the devices and instruments to be interfaced with
heart for diagnosis and treatment. The prevalen
electrocardiography (ECG) today is easy to use but only
retrieves crude signals of overall heart function. Magnetic
resonance imaging (MRI) is a powerful tool for studying heartstructural and motional details and disease mechanisms
However todays MRI systems are bulky, highly complicated
and expensive, and often suffer from limitations in speed and
resolution. We have been exploring a new, low-cost approach
of directly probing heart wall motion by using distributed
surface-mount, and miniaturized (e.g., micro and nanoscale)
electromechanical devices for regional strain/stress and
motion sensing. Here we report our initial effort toward thi
goal, and describe our first experimental results.
Figure 1. A glance of the heart structures and functions from an engineer
viewpoint. (a) Illustration of the anatomy of the heart, showing the heachambers, vessels and valves. (b) Illustraton of the pacemakerand distaconduction system.
II. HEART WALL MOTIONThe heart is an electromechanical organ with great
structural and functional complexities. Its wall motion is
depending upon the compromised coronary arterial supply
Myocardial wall motion defects are essential and sensitive
markers for coronary artery disease and myocardial ischemia
The capability of directly probing regional or highly localized
heart wall motion may also have critical impact on arrhythmia
(a) (b)
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restoring synchronization between asynchronous chambers or
regions, early alarm of regional muscle fatigue or failure, etc.
Figure 2. Simplified illustration of the complexity of the heart wall musclestructure and organization the basket-weavingarthitecture of cardiac musclecells and the myrocardial fibers. (a) A perspective view of the weaving fibersin layers at various depth in the heart wall. (b) A simplified model showingthe weaving structure and orientation.
There are several types of muscle cells that participate in
and coordinate the complex motions in concert. The most
important of these include (i) the cardiac muscle cells
making the weaving myocardial fibers (see Figure 2a), (ii) the
vascular smooth muscle cells (abundant in the coronary
arterial tree), (iii) the conduction system muscle cells (e.g., in
the pacemaker region shown in Figure 1b). For this weaved
basket, advanced MRI techniques including tagging,
harmonic phase, and diffusion tensor MRI (DTMRI) have
been developed for regional wall motion and strain assessment
[4-7]. This work describes our initial effort and preliminary
results toward a convenient electromechanical monitoring and
diagnosis system using piezoelectric (PZE) devices, which,
with computer aid, can automatically detect and monitor local
heart wall motion ex vivo.
Figure 3. Piezoelectric (PZE) cantilever devices for electromechanical signal
transduction. (a) Illustration of a prototypical composite cantilever with anactive PZT layer sanwiched between two thin electrodes (metallic coatinglayers). (b) Simplified illustration of cantilever bending upon application ofexternal force at the cantilever tip.
III. PIEZOELECTRIC CANTILEVERSENSORSA.Piezoelectric Cantilevers
We explore piezoelectric (PZE) device technology because
of the direct electromechanical coupling effect in PZE
transducers. A PZE device as simple as a singly-clamped
cantilever beam (Figure 3) can be conveniently maneuvered to
probe static deflections and dynamic motions of other
mechanical systems. We have been exploring two scenarios
for a PZE cantilever device to interface with a beating heart
(i) making contact between the free end of the cantilever and
regions of interest on the heart wall, while keeping the other
end of cantilever clamped on a solid (not moving) substrate
(ii) mounting the base (clamped end) of the cantilever on the
beating hearts surface and having the cantilever body free to
move and vibrate. The former is suited forex vivo studies; the
latter is attractive for packaged implanted systems.
Figure 3 illustrates a generic cantilever device based upon a
~65Pm-thick PZE lead-zirconate-titanate (PZT) thin filmsandwiched between two metal electrodes, a bottom ~65Pm
thick brass layer, and a top ~15Pm silver coating. We exploi
the d31 coupling in such structures transverse (out-of-plane)
motion of the cantilever tip (free end) induces in-plane strain in
the PZT layer and causes surface charge and electrical potentia
between the two electrodes which is read out for monitoring of
motion. Within the scope of this work cantilever tip in
contact with heart wall with quasi-DC movements (beating
frequency much lower than the fundamental resonance of the
cantilever), the displacement, force, and the voltage signal are
in convenient linear relationship, i.e., VPZEvd31Gvd31F/keffin a simple lumped parameter model [8].
TABLE I. PIEZOELECTRIC MATERIALS OF INTEREST
MaterialPiezoelectric Coefficients
[pm/V or pC/N]
Youngs
Modulus
[GPa]
Density
[g/cm3]
PZTd33~100600, d31~50300
d15~100800~40150 ~7.57.8
ZnO d33~10, d31~4, d15~3 ~30140 ~5.6
AlN d33~5.6, d31~2.6, d15~2.5 ~330410 ~3.26
PVDF d33~2030, d31~20, d15~1040 ~215 ~1.76
Figure 4. The first generation of our prototyped piezoelectric (PZE) devicebased upon flexural-mode cantilevers using PZE thin film materials (e.g., PZTand PVDF). (a) A vibration energy converter in plastic package withcomplementary dual PZT layers, easily generating ~10V level voltage signalsfrom human body movements. (b) A PZT-based device with on-board energyconversion and harvesting circuit. (c) A much thinner PZT-based device. (dA PZE cantilever based on flexible PVDF material. Scale bars 1cm. (eMeasured time-domain voltage waveform (peak voltage ~2V) due to ringdown oscillations of a ~30Hz resonanst mode. (f) Voltage (peak voltage~32V) measured from ~110Hz oscillations. Legend initial tip deflection.
B. Materials of ChoiceWe choose PZT as the active material for its large PZE
coefficient and easy availability for this study. Table I displays
a short list of materials that we find interesting for employmen
in our studies. We have also been exploring devices made o
polyvinylidene fluoride (PVDF) because of its attractive and
promising properties for implants on flexible substrates. Othe
(a) (b)
Base
Apex
Clamping
PZT Cantilever
L
w tTop Electrode
x
y
zBottom Electrode
E Fieldd31 Coupling
F
G0
x
y
(a)
(b)
Clamping Port Silver Coating PZT Layer Brass Electrode
(a) (b) (c) (d)
0.0 0.1 0.2
0
10
20
30
MeasuredSignal(V)
Time (s)
5.08 mm3.81 mm
0.1 0.2 0.3
0
1
2
MeasuredSignal(V)
Time (s)
5.08mm3.81mm3.18mm
(e) (f)
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materials of potential interest include zinc oxide (ZnO) and
aluminum nitride (AlN), particularly for recent developments
in engineering them into micro and nanoscale functional
devices that could be integrated and packaged in implanted
microsystems.
C.Prototyped DevicesWe first demonstrate several prototyped PZE cantilevers
using PZT and PVDF. The prototyped devices (see examples
in Figure 4) are first calibrated in DC/static operation, and are
then extensively tested in pulse and resonant modes. Early
generations of cantilevers are on the few-mm- to 1cm-scale in
size, with fundamental flexural resonance frequencies in the
~0.1kHz to ~1100kHz ranges, and easily generates voltage
signals up to ~10V. Our preliminary data and estimation show
that these devices and their performance can be suited for both
quasi-DC and resonant-mode applications, operating a
atmospheric pressure, either in customized macroscopic plastic
packages, or in micro polymeric thin film packages.
Figure 5. The heart perfusion system for ex vivo experimental studies with the isolated live rat heart. (a) Picture of a prototypical perfused rat heart with surfacemount external bulky electrodes for physiological measurements (e.g., see http//vflab.org). (b) Highly simplified schematic of our experimental approach using boththe external piezoelectric (PZE) devices on heart wall, and the conventional approach for heart function recording system in a canonical rat heart perfusion system. (cIllustration of the scheme of using a balloon ( i.e., simiar to balloon valvuloplasty) and its associated external perssure sensor for heart function recording. (I) and (IIare two specific options for implanting the balloon; we use option (II) in all the tests presented in this work.
IV. EXPERIMENTAL TECHNIQUESIn this early-stage effort of our exploration, as illustrated in
Figure 5, we combine the piezoelectric (PZE) cantilever
monitoring technique with well-established (commerciallyavailable) heart function recording systems. This helps to
reliably evaluate the new approach and calibrate the
measurements and the devices, both qualitatively and
quantitatively, against todays standard protocols.
A.Heart Perfusion System and Heart Function RecordingThe conventional real-time heart function recording is
realized in a heart perfusion system, as illustrated and shown
in Figure 5 and Figure 6. The system is based on the classical
Langendorff technique for isolated heart perfusion [9]. This
allows for convenient and prompt ex vivo studies, and manybrute-force (e.g., Figure 5a) experiments, on isolated hearts.
In the particular case of this study, the perfusion systemgreatly facilitates the continuous tests with the piezoelectric
cantilever probes in a considerably long time (depending on
the heart lifetime in the perfusion system, ~1-3 hours
typically). It provides not only the live heart, but also a
parallel monitoring option as a control experiment.
Male Sprague-Dawley rats of 1012 weeks old are
heparinized (1000 units/kg, i.p.) and anesthetized by sodium
pentobarbital (85 mg/kg. i.p.). The heart is excised, cannulated,
and perfused with Krebs-Henseleit (KH) buffer containing (in
mM) 118.5 NaCl, 4.7 KCl, 1.2 MgSO4, 1.2 KH2PO4, 1.5 CaCl2,
11.1 glucose, and 25 NaHCO3. Isolated hearts are perfused at a
constant pressure in the Langendorff-type perfusion system
The perfusate was maintained at 37C and equilibrated with 95
O2-5% CO2.
Figure 6. Pictures of the rat heart perfusion system employed in this work(a) The overall Langendorff perfusion system with rat heart, pump, circulationlines, the implanted balloon sensor and its data acquisition system (vendorADInstruments). (b) Close-in view of the rat heart in the perfusion buffer.
Embedded in the heart perfusion system, as shown in
Figure 5c, we insert a water-filled latex balloon into the lef
ventricle (i.e., similar to balloon valvuloplasty). The balloon isconnected to an external pressure transducer to record the lef
ventricular developed pressure (LVDP) and heart rate (HR)
The hearts rate-pressure-product (RPP), i.e., the product o
LVDP and HR, is then calculated as an index of the workload.
Heart
Function
Recording
Pressure
Perfusion
System
Heart Wall
Motion
Recording
(b)(a)
Left
Ventricle
Left
Atrium
Right
Atrium
Right
Ventricle
(II)
(I)
Tricuspid
Valve
Mitral
Valve
(c)
(a) (b)
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The measured rat heart rate can typically be in the range of
~150250 bpm (beats per minute) at the beginning of the
experiment (with a fresh and healthily perfused rat heart). The
heart rate decreases gradually as the time elapses. The
temperature of the perfusion buffer is a critical factor for
keeping the heart alive. When temperature deviates, the heart
function could degrade, and the amplitude of heart wall
movement may decrease dramatically. Figure 6 demonstrates
pictures and details of the rat heart perfusion system we have
been implementing in this study.
B.Piezoelectric Cantilever Monitoring SystemWe have built a convenient desktop apparatus for
interfacing the piezoelectric cantilever probes with the rat heart
in the operating perfusion system. Cantilever probes can be
positioned and adjusted by moving the arms (to which the
cantilevers are clamped) on the stage with control in all three
directions. Figure 7 demonstrates a picture of an early
generation of the implementation.
Figure 7. Picture of first-generation exprimental implementation of ex vivomonitoring of rat heart wall motion, by using surface-contacting piezoelectric
(PZE) cantilever probes. For each cantilever, its one end is clamped, and theother end (tip) is in contact with the heart wall muscle. In paralle, theperfused rat hearts basic function is also being monitored using the balloonvalvuloplasty technique. In this particular picture, the free ends of a pair ofcantilevers are gently contacting the left and right ventricle of the heart.
TABLE II. PARAMETERS OF SELECTED TESTED DEVICES
Cantilever Device
ID
Length
[mm]Width
[mm]Resonance
[Hz]
(I)-A 18.0 7.0 222.0
(I)-B 19.0 7.3 214.0
(II)-A1 1.5 0.3
(II)-A2 1.3 0.4
(II)-A3 1.4 0.3
(II)-B1 1.6 0.4
(II)-B2 1.5 0.3 (II)-B3 1.4 0.4
As we expect these cantilever devices to operate while
interfacing with perfused hearts in physiological solutions, we
need to package the devices so that their electromechanical
performance would not be compromised by any corrosion or
contaminants. Prior to testing, every device is coated by a thin
layer of parylene C (thickness on the order of ~5Pm).
We note that in Figure 7 the liquid solution for nurturing
the heart is temporarily moved away. In the present generation
of setup, both the heart and all the cantilevers and device arrays
(all micropackaged with ~5Pm parylene C thin layer) are
immersed in the fluid. Basic parameters of two generations o
devices tested in this work are summarized in Table II.
V. EXPERIMENTAL RESULTS AND DISCUSSIONSExtensive experimental observations and measurements
have been performed. First, the heart function is recorded
using the balloon implanted in the left ventricle, which
provides a reference and calibration for the performance of the
perfused rat heart. Then the piezoelectric cantilevers areapplied to make contact to the heart wall for direct
electromechanical probing.
A.Heart Function Recorded by Balloon in Left VentricleWithout engaging any piezoelectric devices, real-time heat
function is recorded by the left ventricular balloon and its
associated pressure sensor. Typical data traces of LVDP and
left ventricular pressure changing rate dp/dt are recorded for
~12 hours or even longer, throughout the whole lifetime o
the perfused heart. Figure 8 shows the measured data in a very
short 12s time interval. Table III summarizes the results from a
few repeated measurement runs by only using the implanted
balloon for monitoring and recording.
Figure 8. Representative data of the perfused rat heart under healthycondition, measured in real time by only the balloon implanted in leftventricle (no any external cantilever probes touching the heart wall). (a) Lefventricular developed pressure (LVDP, in mmHg) as a fundtion of time. (bMeasured pressure changing rate dp/dtas a function of time.
TABLE III. MEASURED HEART PARAMETERS WITHOUT CANTILEVERS
Test Run
ID
Heart Rate (HR)
[beats per minute, bpm]LVDP
[mmHg]RPP
[mmHgbpm]
1 153 r 3 135 r 2 20655 r 710
2 150 r 3 120 r 2 18000 r 666
3 184 r 5 102 r 2 18765 r 890
B. Measurements with Piezoelectric (PZE) CantileversPrior to using the cantilevers for perfused heart wall motion
probing, we first perform a dry-run test by using air-filled
balloons to mimic simplified heart motions. Because the
fundamental flexural-mode resonance frequencies of the PZT
cantilevers in this work are usually in the range of ~200Hz to
~100kHz range, the rat heart motions are well in the close-to
DC or quasi-DC range. Because in all our tests, the cantilever
are in contact with the air balloon (i.e., heart model) or
perfused heart at the cantilevers tips, the tip motions closely
follow the contractions and heart beat cycles. The heart motion
does not drive the cantilever into its flexural-mode resonance.
0
50
100
150
200
LVDP
(mmHg)
0 2 4 6 8 10 12
-1000
-500
0
500
1000
dp/dt(mmHg/s)
Time (Sec)
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Such quasi-DC operations of the cantilever probes lead to a
simple linear relation between the piezoelectric voltage output
and the detected displacement of heart wall motion. The dry-
run test (using air balloon to simulate a beating heart)
indicates that for the early generations of devices (relatively
large), e.g., both (I)-A and (I)-B (listed in Table II), have high
conversion responsivity (i.e., gain), ~3V/mm (voltage per unit
cantilever deflection at its tip). In both the dry-run with heart
models and the perfused heart tests, the output voltage signals
are directly recorded and monitored by the oscilloscope using
Labview/DAQ software.
Figure 9. Voltage signal measured from a pair of PZT cantilevers touchingthe heart wall. (a) The free ends (tips) of the two cantilevers touching theheart wall of the left and right ventricle, respectively. (b) The free ends of thecantilevers are touching the base and apex of the heart wall, respectively.
Figure 9 demonstrates the voltage signals representing the
local heart wall motions, probed by a pair of PZT cantilevers.
In all these cases, the free ends of the cantilevers just barely
touch the heart wall. When the cantilevers tips make contact
to the left and right ventricles (Figure 9a) respectively, the
extracted heart rate is HR~229bpm. Measured voltage signal
is Vpp~150mV, and ~350mV, for device (I)-A and (I)-B
respectively. The asymmetry in the data amplitude from this
pair of devices is due mainly to the fact that one cantilever
device has been pre-bent (with a transverse crack developed
but not yet broken, at ~1/3 length near the clamped end), and
thus has much less strain developed given the same
displacement at the tip. When the devices tips are placed
against the base and the apex at a later time, the data show a
lower HR~43bpm, and lower Vpp~50mV and 150mV,
respectively, mostly due to the heart degradation during thetime of transition.
The effects of probing the heart wall motion by making
contacts with different depths and strengths are also explored.
A second generation (group (II) listed in Table II), smaller
cantilevers, in small parallel fingers-alike arrays, are used.
With control of the positioning arms, the devices are first
carefully placed to just barely touch the heart wall, and then
gradually move toward the heart center to start gently pressing
the heart wall. Figure 10 displays the measured data from a
pair of small cantilevers, (II)-B1 and (II)-B2, in contact with
the heart wall under three different depth/strength conditions.
Figure 10. Voltage signal measured from a pair of smaller cantilever devices
with varying the depth of the cantilever tip touching the heart wall. (a) Datfrom device (II)-B1. (b) Data from device (II)-B2. The data shown artruncated from much longer traces. For each device, data for three contacconditions are taken at three time intervals in series. Throughout these time
intervals, the implanted balloon recording ensures that the heart functions arenormal and stable. The offsets on the time axes are not adjusted among thdifferent traces.
In case of just touching but not pressing the heart wall
larger devices (group (I) in Table II) yield larger Vpp, which is
evident from Figure 9 and Figure 10. As cantilever tips get to
press against the heart wall gradually, the signals first increase
as expected, and then there is no more appreciable signa
increase observed with further pressing of the devices against
the heart surface. Such information can help us better
understand the strength of the heart wall motion, especially
with more advanced future generations of devices. We also
note that the data traces from larger devices (gently touching
heart wall, Figure 9) appear to be proportional to the dp/ddata in Figure 8, while the voltage signals from the smaller
devices (under all contact conditions, see Figure 10) seem to
have the shape similar to that of the LVDP curve in Figure 8
We are currently making more effort to investigate this
intriguing phenomenon.
As we aggressively miniaturize these devices by using
micromachining techniques, their apparent signal levels
decline. Nonetheless, with significant volume reduction they
become better suited with flexible substrates [10,11] and
packages that are more amenable to harsh environments for
implants in living bodies. We envision that it is also possible
for us to take advantage of the resonant operations of the PZE
devices, combined with air-cavity packages possible inflexible substrate, cantilever- and membrane-structured
micro/nano resonators in various frequency ranges can be
exploited for local heart wall motion monitoring. Further, the
same types of PZE devices in micropackages can also be
employed for energy conversion from heart beats [12], which
could be exploited for self powering low-power implants
Moreover, for miniaturized devices and chip-scale implants
the signal transmission could be not only wired but also
wireless. As all these technical components are getting ready
the approach of using miniaturized PZE devices explored in
this work can lead to both external heart function monitoring
systems in research and clinic labs (e.g., supplementing the
3 4 5 6 7 8 9-0.2
-0.1
0.0
0.1
0.2
VoltageSignal(Volt)
Time (Sec)
Device (I)-BDevice (I)-A
2 3 4 5 6-0.2
0.0
0.2
0.4
VoltageSignal(Volt)
Time (Sec)
Device (I)-BDevice (I)-A
(a)
(b)
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
-0.2
0.0
0.2 Just Touching Heart WallTouching & Gently Pushing WallPushing Harder on Heart Wall
VoltageSignal(Volt)
Time (Sec)
0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4
-0.2
0.0
0.2 Just Touching Heart WallTouching & Gently Pushing WallPushing Harder on Heart Wall
VoltageSignal(Volt)
Time (Sec)
(a)
(b)
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conventional implanted balloon recording), and implanted
systems for surgery and patients chronic heart monitoring
and in all these applications, capable of offering high
sensitivity and high spatial and temporal resolutions for
parallel readout of heart wall motion at various locations.
VI. CONCLUDING REMARKSIn summary, we have shown that using external surface-
contact or surface-attached piezoelectric (PZE) cantilevers can
probe the rat heart wall motion and the heart function ex vivo.The cantilevers in the present work are made of PZT thin films
with strong PZE effect. The d31 coupling effect in the
cantilever is exploited to transduce the flexural mechanical
motion of the cantilever into electrical signal for readout. The
cantilevers have been limited to quasi-DC operation (heart
beating rate much lower than cantilevers resonance frequency)
with their tips closely following the movements of the regional
heart wall. Devices with sizes in the mm-scale and sub-mm-
scale are tested. The preliminary tests verify the feasibility of
monitoring heart wall movements with good resolutions in the
time domain, and at different locations on heart surface. The
heart wall displacement extracted from the measurement is
typically ~0.10.3mm, which is consistent with MRImeasurement. The output power level of typical PZE
cantilevers we have tested is in the range of ~110:
Combined with advances in PZE materials at micro and
nanoscale, implantable and flexible materials, and
micropackaging techniques, this approach is expected to have
the potential of being implanted, as well as offering very high
spatial and temporal resolutions by employing further
miniaturized devices.
ACKNOWLEDGMENT
We thank the Louis Strokes Cleveland Medical Center of
the Department of Veterans Affairs and the Case School of
Engineering for financial support. We are indebted to C. A.Zorman, M. A. Rogonjic, and K. N. Kortepeter for their
administrative support. We are grateful to the IEEE UFFC
IFCS/EFTF 2011 for the Student Travel Support Award (for
R.Z.). We thank R. C. Roberts and S. B. Lachhman for help on
materials and instruments.
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