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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
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High Peak SAR Exposure Unit With Tight Exposure
and Environmental Control for In Vitro
Experiments at 1800 MHz
Jürgen Schuderer, Theodoros Samaras, Member, IEEE, Walter Oesch, Denis Spät, and Niels Kuster, Member, IEEE
Abstract—The objective of this study was to develop, optimize,
and characterize a flexible and reliable unit for standardized and
well-controlled electromagnetic-field exposure of cells in vitro.
The technical requirements were high peak and time-averaged
exposure of the cells with a minimal temperature rise for the cell
cultures, flexible modulation schemes, high uniformity, and low
variability of exposure, as well as support of blinded protocols.
The developed setup is based on two R18 waveguides resonant
at 1800 MHz and operated with a computer-controlled signal
and monitoring unit. The cells can be exposed in 35-mm Petri
dishes either cultivated as monolayers or in suspension. For cell
monolayers, the system provides an efficiency for the specific
absorption rate (SAR) of 50 (W/kg)/W input power, a nonuniformity of the SAR distribution of 30%, SAR variability of
6%, and a temperature rise of 0.03 C/(W/kg) average SAR.
For cell suspensions and provided that the cells are not in the
meniscus area, a SAR efficiency of 10 (W/kg)/W, nonuniformity
of 40%, SAR variability of 17%, and a temperature rise of
0.13 C/(W/kg) is achieved. The numerical dosimetry for the
field and temperature distributions within the Petri dishes was
verified using -field and temperature probes. The temperature
analysis has shown that the possibility of localized “hot spots” can
be excluded.
Index Terms—Dosimetry,
absorption rate (SAR).
exposure
setup,
RF,
specific
I. INTRODUCTION
I
N VITRO studies are important for the detection of the
biological effects of RF electromagnetic field (EMF) exposures, e.g., as emitted by mobile phones. They can be used
to identify basic mechanisms and to analyze functional and
structural changes in living cells. The objective of this study
was to develop a standard in vitro exposure system operating
in the digital communication system (DCS) frequency band
of the global system for mobile communications (GSM) at
1800 MHz. The setup shall be used for various diverse study
endpoints by a multitude of laboratories working within the
European research program. Therefore, the setup should fit
inside commercial incubators and needs to provide high flex-
Manuscript received October 15, 2003; revised March 23, 2004. This work
was supported by the Swiss Agency of Education and Science, by the Mobile
Manufacturers Forum, by the GSM Association, and by Sunrise TDC.
J. Schuderer, W. Oesch, D. Spät, and N. Kuster are with the Foundation
for Research on Information Technologies in Society, Integrated Systems
Laboratory, Swiss Federal Institute of Technology, CH-8092 Zürich,
Switzerland (e-mail: [email protected]).
T. Samaras is with the Department of Physics, Aristotle University of
Thessaloniki, 54124 Thessaloniki, Greece.
Digital Object Identifier 10.1109/TMTT.2004.832009
ibility with respect to different exposure schemes and cell
culturing conditions. Among the anticipated conditions, cells
might by cultivated as a monolayer on an artificial substratum,
e.g., the plastic bottom of a Petri dish, or might be grown in
suspension, such as blood cells in plasma. In particular, the
following requirements for the RF exposure system posed by
the European research program consortia were derived from
[7].
• SAR Requirements. 1) The temperature rise of the cells
as a result of the exposure should be insignificant (i.e.,
0.1 C) for levels of the specific absorption rate (SAR)
as high as the International Commission for Non-Ionizing
Radiation Protection (ICNIRP) limit for local exposures
set for the general population, i.e., SAR of 2 W/kg [5].
2) The setup needs to provide high SAR efficiency since
exposures at this level with signals of high crest factors1
demand high peak SAR exposures (e.g., 150 W/kg for
the discontinuous transmission mode (DTX) of GSM).
3) The nonuniformity of the SAR over all cells should be
less than 30% (minimal sample area for cell monolayers:
50 cm , minimal sample volume for cell suspensions:
10 mL). 4) The combined uncertainties of the SAR
assessment and possible exposure variability due to drifts
and other variations between different experiments should
not dominate the SAR nonuniformity, i.e., should be less
than 30%. 5) The power isolation between exposure and
sham must be more than 30 dB.
• Signal Requirements. A flexible signal unit is required to
enable complex modulation such as: 1) continuous wave;
2) pulse or sinusoidal modulation at any frequency and
repetition rate; 3) GSM signals simulating: i) the basic
GSM mode (basic) active during talking into the phone,
ii) the DTX mode active while listening, iii) conversation
covering temporal changes between basic and DTX, and
iv) network environment covering environmental power
control and handovers; 4) other time division multiple
access (TDMA) signals such as digital advanced mobile phone service (DAMPS), digital enhanced cordless
telephone (DECT), personal handyphone system (PHS),
etc. Additionally, intermittent exposure protocols with
intermittence cycles from seconds to hours should be
applicable.
• Controlling Requirements. Identical environmental parameters for exposure and sham must be ensured, i.e., both
1Crest
factor
0018-9480/04$20.00 © 2004 IEEE
= ratio
between the peak and average SAR.
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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
systems should be kept in the same incubator and temperature differences between exposure and sham should be
less than 0.1 C. Blinded protocols should be applicable,
and the exposure and environmental conditions must be
continuously monitored. The setup should be capable of
self-detecting malfunctions.
• Requirements for Dosimetry. The dosimetry should
cover: 1) detailed numerical evaluation of the SAR distribution; 2) experimental verification by dosimetric measurements; 3) uncertainty and variability analysis for the
SAR; and 4) evaluation of the temperature rise during
exposure.
Different setups have been used in the past for the exposure
of cell cultures at the 800- and 900-MHz cellular frequency
bands: Transverse electromagnetic (TEM) cells (e.g., [11], [6],
[13]), RF chambers [9], radial transmission lines (RTLs) [10]
and wire-patch systems [8]. Rectangular waveguides were employed in [17] for the DCS frequency band, and cylindrical
waveguides were applied in [3] for personal communication services (PCS).
Schönborn et al. [16] have qualitatively compared the performance of the TEM cell, RF chamber, RTL, wire-patch cell, and
waveguide. For setups operating in the 1800-MHz region, the
following conclusions can be drawn with respect to the formulated requirements, which are: 1) the RF chamber in -polarization cannot fulfill the requirements for SAR uniformity, SAR
efficiency, and small size to fit inside an incubator. 2) The RTL
setup provides good performance for studies with large sample
volumes; however, it must be excluded for this study due to high
costs and efforts to provide the required peak SAR and environmental control. 3) The waveguide setup operated at a cavity resonance can be expected to fulfill the requirements. It should provide: i) high SAR efficiency due to resonant operation; ii) small
temperature rise for cell monolayers (low SAR for the whole
medium at high SAR for the monolayer); iii) good uniformity
of SAR when the Petri dishes are exposed in -polarization;
and iv) good environmental control because exposure and sham
chambers can be placed in the same incubator.
Consequently, the developed setup is based on waveguide
cavities that were optimized for cell monolayer exposures. In the
course of the research programs, however, additional biological
experiments have been added, requesting the exposure of cells
cultivated in suspensions. For that purpose, a new configuration
was developed enabling the exposure of cells in suspension with
reasonable uniformity.
Fig. 1. Side view of geometry and functional parts of the exposure system. The
configuration for the cell monolayer is shown (all dimensions in millimeters).
Inner dimensions of the R18 waveguides: 64.8 129.6 425 mm (height
width length).
2
2
Fig. 2.
2
2
Exposure chambers with removed end-short plate.
carrier frequency, which approximates exposure from mobile
communication systems like DCS (uplink: 1710–1785 MHz;
downlink: 1805–1880 MHz), PCS (uplink: 1850–1910 MHz;
downlink: 1930–1990 MHz), and universal mobile telecommunication system (UMTS, uplink: 1920–1980 MHz; downlink:
2110–2170 MHz).
B. Waveguide Cavity
II. DESIGN OF THE SETUP
Figs. 1 and 2 show the mechanical design of the realized
exposure system. The concept is derived from [17]. Novel
features have been developed and implemented to meet the
requirements:
A. Frequency
R18
instead
size of
length:
waveguides (cross section: 129.6 mm 64.8 mm)
of the R16 waveguides [17] were used to reduce the
the entire setup (height: 450 mm, width: 200 mm,
500 mm), but still enable the exposure of cells at a
The waveguide and coupler were optimized to achieve a resonance with minimal field disturbance inside the waveguide
cavity. This was achieved by adjusting the length for a resonator
mode at 1800 MHz. A flat loop coupler (Fig. 3) on one end
of the waveguide and an end-short plate on the other end were
gold plated to ensure good RF contacts. The short plates were
equipped with quick-mounting fasteners in order to allow access
to the cavities. The loop coupler has the comparable advantage
over the monopole -field coupler in that it reduces the extension of the evanescent mode region and, therefore, enables utilization of a larger proportion of the waveguide or a reduction
of the length.
SCHUDERER et al.: HIGH PEAK SAR EXPOSURE UNIT WITH TIGHT EXPOSURE AND ENVIRONMENTAL CONTROL FOR IN VITRO EXPERIMENTS
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an entire cultivation area of 60 cm are exposed to a uniform
SAR distribution.
D. Exposure of Cell Suspension
Fig. 3. Side view of the loop coupler used for excitation of the waveguide
cavities.
Fig. 4. Petri dish holders for cell monolayer and cell suspension exposure.
Dishes are placed inside the H -field maxima for monolayer and inside the
E -field maxima for cell suspension cultures.
TABLE I
POSITION OF THE PETRI DISHES INSIDE THE R18 WAVEGUIDES
The cavity loading is not significantly affected by the insertion of the Petri dishes ( -factor unloaded cavity 4000 versus
-factor loaded cavity 1500). The 3-dB resonance bandwidth
of the loaded cavity depends on the amount of cell medium in
the Petri dishes and is in the order of 1–2 MHz, which is sufficient for all TDMA signals.
The exact resonance frequency is determined prior to exposure by a frequency sweep for maximum field strength at the
monopole field sensor. The narrow-band resonant design increased the SAR efficiency by a factor of 30 compared to [17],
i.e., 50 (W/kg)/W input for 3 mL per dish. For cells in suspension, the efficiency is 10-(W/kg)/W input for 3.1 mL per dish.
C. Exposure of Cell Monolayer
Six 35-mm-diameter Petri dishes (effective inner diameter:
33 mm) are placed in the -field maxima of the standing waves
(two dishes per maximum). A dish holder (Fig. 4) and distance
keeper ensure the correct placement inside the waveguides and
minimize spatial variability with respect to the incident fields
(position accuracy for Petri dishes: 2 mm). The distances of
the dishes to the short are given in Table I. Cell monolayers with
Cell suspensions are exposed in the -field maxima of the
resonator because a pure -field coupling is expected to result
in a uniform SAR for a thin and flat dielectric (as for the
suspended cell medium in the Petri dish). Four 35-mm Petri
dishes, providing a sample volume of 12.4 mL are used (for
positioning, refer to Table I). Due to stray fields in the proximity
of the Petri dishes, the -field maximum at the field sensor
location was not used for loading. Since strong coupling at the
sides of the dishes is present, uniformity of the SAR is increased
by the following loading procedure (Fig. 4): 35-mm-diameter
dishes filled with 3.1 mL (liquid height: 3 mm) of medium
are placed inside 60-mm-diameter Petri dishes (effective inner
diameter: 54 mm). The resulting area between the dishes is
filled with 4.9 mL of distilled water (maximum water volume
to ensure no contact between water and Petri dish cover). A
similar method was used in [8]. As for monolayer exposure,
accurate positioning of the dishes ( 2 mm) is achieved by
using a dish holder and distance keeper.
E. Exposure Control
Input power measurements provide poor accuracy for
resonant structures and have been replaced by actual field
measurements inside the waveguide. Since the cavity loading
is low, measurement of the - or -field at one location only
is sufficient to assess the incident exposure of all Petri dishes.
The optimal solution would be a loop antenna at the short, since
here, the location of the -field maximum is not dependent
upon the wavelength. To avoid damage during loading of the
dishes, a mechanically protected monopole antenna at the
location of the first -field maximum before the short was preferred. Its length of 2.5 mm was optimized to cover a dynamic
range of 50–10 000 V/m, 0.1–20 A/m when directly connected
to a Schottky-diode detector (ACSP-2663NZC15, Advanced
Control Components, Eatontown, NJ). The monopole and
diode detecter were calibrated against an H3DV3 -field probe
(SPEAG, Zürich, Switzerland) positioned at the location of an
-field maximum. A low-pass filter is applied at the dc output
of the diode to suppress noise.
F. Signal Generation
A fully computer-controlled signal unit was realized (Fig. 5).
It is based on an RF signal generator (SML02, Rhode &
Schwarz, Ittigen, Switzerland), an arbitrary function generator
(33120A, Agilent Technol., Palo Alto, CA), a 5-W power
amplifier (LS Electronik AB, Spanga, Sweden), a self-built
radio frame generator and a data logger (34970A, Agilent
Technol.). The general-purpose interface bus (GPIB) is used
for software communication with the devices. Modulation can
be applied in the following three pathways.
1) Amplitude modulation (AM) of the RF generator by the
arbitrary function generator: any signal with a waveform
length of 16 000 points, an amplitude resolution of 12 bits,
and a frequency of less than 15 MHz can be used.
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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
TABLE II
MATERIAL PARAMETERS USED IN THE SIMULATION (" : RELATIVE
PERMITTIVITY, : ELECTRIC CONDUCTIVITY, c: SPECIFIC HEAT
CAPACITY, k: THERMAL CONDUCTIVITY, : MASS DENSITY)
Fig. 5. Signal generation and monitoring unit (H: H -field, T: temperature,
I : fan driving current, DL: data logger, PC: personal computer).
2) Software control of the output power of the RF generator:
allows arbitrary field on/off intermittency and arbitrary
power variations.
3) Blanking of the amplifier with the radio frame generator:
is used to achieve idle frames; temporal changes between
different radio frame structures can be realized.
The data logger is used for the collection of all sensor signals and for the generation of digital control signals, e.g., for
switching the microwave relay (SR-2MIN-D, RLC Electronics,
Mount Kisco, NY). The measured field values are used for feedback regulation of the output power of the RF generator. In this
way, amplifier drift and variations are compensated.
G. GSM Signals
The described concept is used for GSM modulation in the following way. The GSM burst, defined according to [2], is stored
at the function generator and is applied to the AM modulation
input of the RF generator. The frame structures of the basic
crest factor
and DTX crest factor
modes
are stored on the radio frame generator. Switches between both
frame structures are software controlled and carried out by the
data logger. Software regulation of the output power of the RF
generator according to statistical functions is used to simulate
the environmental events of a GSM phone conversation like
channel fading, handovers, etc. The digital Gaussian mean shiftkeying (GMSK) modulation of the GSM signal is not applied
since it has not been considered of significance for possible
bio-responses. However, a vector RF generator can be easily
integrated.
H. Environmental Control
Good environmental control is achieved by operating both
waveguides inside the same incubator and enforcing rapid air
exchange by fans (612NGHH, Papst, St. Georgen, Germany: air
flow 56 m /h). However, it is not sufficient to place the waveguides next to each other since incubators can have a significant temperature gradient of several tenths of a degree. The
requirement of less than 0.1 C difference between two unexposed waveguides is, therefore, only possible if the air used for
atmospheric exchange for both waveguides enters from the same
location within the incubator, e.g., by arranging the air inlets
close to each other (see Fig. 1).
I. Quality Control
Quality control of the experiments is ensured by monitoring
the exposure and environment, self-detection of malfunctions,
and by blind protocols as follows.
• Monitoring: The sensor signals ( -field, air temperature,
fan driving currents) are continuously recorded by the
data logger with a sampling rate of 0.1 Hz. All experimental data (settings, software commands, sensor signals)
are stored in a file on the PC.
• Blind Protocols: Blind study design is realized by randomly switching the microwave relay prior to exposure.
Data files, including the information on which of the
waveguides was exposed, are encoded. Decoding can
be carried out by a dedicated program after biological
evaluation.
• Self-Detection of Malfunctions: The controlling and monitoring software is able to self-detect malfunctions and responds with warnings or shut-down if required (tracing
and handling of 60 errors). A watchdog for PC shutdown
was realized that does not allow any exposure without software control.
III. METHODS
A. Numerical Methods
New dosimetric methods compared to [17] were applied:
1) Numerical Modeling: Field, SAR, and temperature
distributions were characterized with a full three-dimensional
(3-D) electrothermal finite-difference time-domain (FDTD)
analysis using the simulation platform SEMCAD (SPEAG).
The waveguide geometry was simulated with all dielectric
materials, i.e., supporting plastic parts, Petri dishes, cell
medium [Dulbecco’s modified eagle’s medium (DMEM)],
and distilled water. The corresponding material parameters are
summarized in Table II. As demonstrated in [18], reliable data
can only be obtained if the meniscus profiles at the solid/liquid
boundaries are modeled accurately. Therefore, all simulations
have been performed with meniscus models based on the
profile functions given in [18]. Four different medium volumes
in the range from 2.2 to 4.9 mL (2–5-mm liquid height) were
simulated for cell monolayer exposure. For cell suspensions,
only one configuration with 3.1-mL DMEM and 4.9-mL
distilled water was evaluated. A graded mesh with voxel sizes
between 0.3–5 mm was applied for the discretization of the
numerical model. A waveguide port was used for excitation
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TABLE III
HEAT-TRANSFER COEFFICIENTS FOR THERMAL BOUNDARIES
(for the assessment of SAR uncertainties, the loop coupler
has also been simulated). Only a single total reflection at the
short was simulated (results in the same standing-wave field
distribution as for the resonator); the open free-space region
at the source was terminated with absorbing boundaries. SAR
-field value at a reference
values were normalized to the
position ( -field maximum at the short).
2) Numerical Evaluation:
• Cell Monolayer: The cell monolayer is numerically represented as the interface between the FDTD voxels of the
cell medium and Petri dish. Since fields at voxel edges
cannot be directly derived from the FDTD implementation
of SEMCAD, extrapolation of the SAR was used to assess
an average value for the monolayer: the SAR values of all
horizontal voxel layers within the cell media were evaluated, leading to an average SAR at a vertical distance ,
which is the distance between the voxel center and monolayer. Second-order polynomial functions were applied to
.
extrapolate the data to
• Cell Suspension: SAR values were evaluated for the entire medium and for the medium excluding the meniscus
(useful value for cells that are not in the meniscus).
FDTD corner voxels at curved Petri dish/media interfaces
were not considered for the evaluation because they are sensitive to numerical staircasing artifacts. The nonuniformity of the
SAR distribution was quantified by the standard deviation of
the SAR distribution and is expressed in relation to the average
value. The lowest voxel layer of all six dishes was evaluated to
derive the monolayer standard deviations, and all voxels representing the medium were used for suspension. The -field was
additionally evaluated with the same methods in order to calculate the field impedance.
3) Thermal Simulation: A thermal FDTD analysis was performed for a single Petri dish model only (simulation of the
entire setup geometry exhausts the computational resources).
This model was analyzed for exposure inside a standing wave
-field maximum for cell monolayers and -field maximum
for cell suspensions. The standing wave was generated by two
incident plane waves. This exposure configuration results in a
similar SAR distribution as for the waveguide. Heat transfer due
to conduction, radiation, natural convection, and forced convection was considered by solving the heat diffusion equation on the
FDTD grid and by applying the appropriate thermal boundary
conditions [15]. Combined heat transfer coefficients for convection and radiation were used to simulate the boundaries [1]. The
coefficients were derived from a flat plate approximation of the
cell medium [4]. The values of the heat transfer parameters are
given in Table III.
B. Experimental Methods
The DASY3 near-field scanner (SPEAG) equipped with dosimetric field and temperature probes was used for field verification and for the determination of the temperature rise in the
medium. Three-axis - and -field probes (SPEAG, EF3DV2,
H3DV6) have been used to determine the incident field distribution in the vicinity of the Petri dishes.
1) SAR Verification: Different methods for SAR verification
were applied as follows.
• Monolayer Exposure: For cell monolayer exposure, a
1-mm-diameter -field probe [14] was used to map a
vertical line in the center of the cell medium (4.9-mL
DMEM).
• Suspension Exposure: For suspension exposure, only
single point temperature measurements were evaluated
-field measurements were
because the dosimetric
considerably distorted by the strong incident -field
parallel to the probe, leading to boundary effects and
immersion depth errors [19]. The method of positioning
the temperature probe (see below) did not allow the
mapping of several points in the medium. During the
SAR measurement, the fans were not operating. The first
50 s of exposure were evaluated by linear regression in
order to derive the local SAR (via
dT/dt). The
temperature increase during this period was only 0.1 C;
however, it was still enough for accurate evaluation because of the low noise level 0.005 C of the temperature
probe (SPEAG, T1V3 thermistor). The 50-s evaluation
period was assumed to be free of possible artifacts
caused by thermal diffusion because SAR gradients in the
vicinity of the sensor are very low and because the double
layer of plastic provides good heat isolation toward the
environment.
2) Temperature Rise: For the assessment of the temperature
rise for the cells, measurements were performed within a
37 C, 95% humidity incubator environment. The probe
was fixed inside the medium, 1 mm above the dish bottom.
For the suspension geometry, the probe was carefully oriented
perpendicular to the incident and induced -fields, which
minimizes RF pick-up at the sensor leads. Additionally, a second
probe was used with its leads guided in parallel to the first one,
but placed below the Petri dish in the air. In this way, possible
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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
Fig. 6. Simulated SAR distribution for monolayer and suspension exposure at 1800 MHz. Data is shown: (a) in a vertical plane in the center of the Petri dish,
(b) in the lowest voxel layer (z
0:15 mm), and (c) in a histogram.
=
TABLE IV
DOSIMETRIC DATA FOR THE AVERAGE SAR, NONUNIFORMITY OF THE SAR DISTRIBUTION, AVERAGE IMPEDANCE, TEMPERATURE RISE,
AND THE CHARACTERISTIC TEMPERATURE RISE-TIME CONSTANTS FOR MONOLAYER (Ml.) AND SUSPENSION (Su.) EXPOSURES
RF pick-up is similar for both probes and is compensated
by differential temperature evaluation. No such artifacts are
present for the monolayer configuration because the probe
was located in an incident -field minimum. Measurements
were performed at SAR levels of approximately 50 W/kg
(monolayer) and 9 W/kg (suspension), resulting in an increase
of approximately 1 C. The values were linearly scaled down
with the SAR and normalized to 1-W/kg average SAR. The
data for the temperature response of the medium was used
for the determination of the maximum temperature rise at
steady state and for the determination of the characteristic
temperature rise-time constants. The latter allows assessment
of the temperature time course for short periods or intermittent
exposures.
IV. RESULTS
A. SAR Characterization
Fig. 6(a)–(c) shows the SAR distribution for monolayer and
suspension exposures in a vertical cut through the dish center,
for the lowest voxel layer in the medium (monolayer only), and
within a histogram, respectively. The internal - and -field
are perpendicular to each other and polarized in the plane of the
monolayer for the monolayer exposure. In contrast, the internal
SCHUDERER et al.: HIGH PEAK SAR EXPOSURE UNIT WITH TIGHT EXPOSURE AND ENVIRONMENTAL CONTROL FOR IN VITRO EXPERIMENTS
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Fig. 7. Simulated SAR and steady-state temperature distributions (start temperature: 37 C, forced air-cooling active). The steady state is reached after
approximately 15 min for monolayer and 30 min for suspension exposure. The location of the temperature probe used for the experimental assessment is
indicated in this figure.
-field is polarized perpendicular, and the -field is polarized
parallel to the medium surface for cell suspensions.
Statistical data for the exposure is given in Table IV: results
for the average SAR values, nonuniformity of the SAR distribution, average field impedance, temperature rise, and thermal
response time constants are reported. The exposure is strongly
dependent upon the medium volume for cell monolayers and is
characterized by high vertical SAR gradients. If cells are not
in the meniscus area, an evaluation of SAR in the medium excluding the meniscus is appropriate and leads to much lower
nonuniformity of SAR for cell suspensions (40% versus 117%).
The field impedance for monolayer exposure is by a factor of
five lower than for suspension.
B. Temperature Rise
A much lower temperature rise is present for monolayer
exposure compared to suspension [3.1 mL: 0.022 versus
0.13 C/(W/kg)]. Fig. 7 shows the simulated SAR and
steady-state temperature distributions for a 1-W/kg exposure
(single Petri dish model). Temperature is uniformly distributed
without localized temperature “hot spots” for both cell culture
configurations. For cell monolayers, the location with the
highest temperature rise is the center of the dish (which was
also experimentally assessed). The probe was not placed within
the temperature maximum during the measurements in cell
suspension. Therefore, the simulated maximum temperature
rise in the meniscus, which is 20% higher, is additionally given
in Table IV. Fig. 8 shows the measured time response curves
for a 51-W/kg monolayer and 9-W/kg suspension exposure.
Fig. 8. Measured temperature rises during RF exposure for cell monolayer and
suspension (3.1-mL cell medium, forced air-cooling active). The temperature
probe was positioned inside the medium, 1 mm above the Petri dish bottom, for
both configurations. The start temperature was 37 C. Average SAR values of
51 and 9 W/kg were present for the cell monolayer and cell suspension (without
meniscus), respectively.
C. SAR Verification, Dosimetric Uncertainty, and Variability
The measured SAR distribution for cell monolayers is compared to simulations in Fig. 9. Measurement data is plotted for
the three upper dishes, as well as for one lower dish. An average difference between simulation and measurement of 15%
was found. For the cell suspension configuration, this difference
for the single-point evaluation was 22%.
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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
Fig. 9. SAR values as a function of the distance to the dish bottom for cell monolayer exposure. The corresponding slots are indicated in Fig. 1.
TABLE V
UNCERTAINTY ANALYSIS FOR THE SAR ASSESSMENT OF MONOLAYER (Ml.)
AND SUSPENSION (Su.) EXPOSURES. ESTIMATED STANDARD DEVIATIONS
WERE DERIVED AND ARE COMPARED TO THE DIFFERENCE
BETWEEN MEASUREMENT AND SIMULATION
These results must be discussed together with the uncertainties of the SAR assessment, as summarized in Table V. Uncertainty was evaluated according to the methodology of [12].
Normal or rectangular error distributions were assumed in order
to derive an estimated standard deviation for each investigated
uncertainty contribution. Combined uncertainties of 20% and
21% are specified for cell monolayer and suspension SAR assessment, compared to the average differences of 15% and 22%,
as derived above. Since the difference is in the range of the
uncertainties, the measured results verify the numerical assessment and support the reliability of the dosimetry.
An analysis of SAR variability is provided in Table VI. A
combined relative variability of 5.1% and 17% in relation to
23%–30% and 40% SAR nonuniformity is derived for monolayer and suspension exposures, respectively.
V. DISCUSSION
A. SAR Efficiency and Uniformity
Both setups provide an excellent SAR efficiency of 50
and 10 (W/kg)/W for monolayer and suspension exposures,
respectively, which is a clear advantage compared to other
exposure systems. An inexpensive 5-W power amplifier is
thus sufficient to achieve monolayer SAR values 200 W/kg.
Signals with high crest factors such as the GSM DTX mode
can be applied at the ICNIRP limit of 2 W/kg. However, the
resonant operation also leads to some disadvantages: The carrier
frequency is not fixed, but depends on the loading volume
of the Petri dishes (1% difference for 2- and 5-mL medium
volume). Secondly, amplitude and phase distortions can occur
due to the restricted resonance bandwidth of 1–2 MHz. This
problem is of no concern for the applied amplitude-modulated
carrier signal with sidebands as multiples of only 217 Hz.
Furthermore, only low distortions are present for a GMSK
modulated GSM signal since its signal bandwidth of 200 kHz
is still 5–10 times less the resonator bandwidth. However,
the application of UMTS signals, which have a bandwidth of
5 MHz, is not possible under resonant conditions. For this
case, a broad-band coupler, as applied in [17], should be used.
The required uniformity of SAR with deviations 30% is
only achieved for cell monolayer exposure and is in the same
order of magnitude as for other exposure systems in the literature. The suspension configuration exceeds the requirement of
a value up to 40% (without meniscus evaluation). If cells do
not settle from the meniscus, a high nonuniformity of 117% is
present (Table IV). Therefore, the sedimentation behavior of the
cells must be analyzed carefully, and exposure should not be
started until cells have settled from the meniscus. The provided
sample area/volume with uniform exposure of 60 cm for cell
monolayer and 12.4 mL for cell suspension is not superior compared to other systems. However, it was chosen in order to keep
the dimensions of the setup small. For studies requiring a higher
sample volume, usage of other setups such as the RTL should
cm ).
be considered (sample area
B. Dosimetric Uncertainty
The dosimetry led to uncertainties for the SAR assessment
of approximately 20% with the highest contributions resulting
from the measurement of the dielectric parameters and the
SCHUDERER et al.: HIGH PEAK SAR EXPOSURE UNIT WITH TIGHT EXPOSURE AND ENVIRONMENTAL CONTROL FOR IN VITRO EXPERIMENTS
2065
TABLE VI
VARIABILITY ANALYSIS FOR MONOLAYER (Ml.) AND SUSPENSION (Su.) EXPOSURES. ESTIMATED STANDARD
DEVIATIONS WERE DERIVED AND ARE COMPARED TO THE NONUNIFORMITY OF THE SAR DISTRIBUTION
calibration of the monopole sensor (Table V). Although no
detailed uncertainty analysis is provided for other setups in
the literature, the exposure characterization reported in this
manuscript should provide a high level of accuracy compared
to others because: 1) meniscus models for the cell media were
used; 2) incident field instead of power monitoring is applied;
and 3) simulations were successfully verified by measurements.
Additionally, for the first time, a full 3-D thermal analysis was
performed to assess the temperature rise in the Petri dishes.
This method allows clear interpretation of the biological results
with respect to thermal or nonthermal effects.
C. Temperature Rise
Continuous exposure with a negligible temperature rise
(
C) can be performed up to 4.5 W/kg for cell
monolayers, but only up to 0.8 W/kg for cell suspensions (SAR
average without meniscus). The small temperature rise of the
monolayer exposure results from the low SAR of the medium
(compared to the monolayer) and from the efficient cooling
(maximum SAR is located at the medium/dish interface, where
heat can be efficiently removed). It is both advantageous and
unique that the monolayer exposure achieves the ICNIRP limit
of 2 W/kg without introducing active liquid cooling based on
an external medium at a different temperature. Active liquid
cooling requires a considerable engineering effort to guarantee
the same absolute temperature for the cells in sham and
exposure and will additionally introduce temperature gradients
in the medium. However, for experiments with SAR levels in
the order of the occupational limits, i.e., at 10 W/kg or higher,
a setup with active liquid cooling is required.
Theoretically, the temperature gradient developed between
the surface and bottom of the exposed cell medium for monolayer exposure can induce mass convection within the liquid
volume. However, such a temperature gradient exists only for a
short period of time because it is quickly equalized by heat conduction. Moreover, if it is combined with the low height of the
medium, it is unlikely to result in mass movement. The product
of the Grashof and Prandtl numbers is an indicator for liquid
convection phenomena [4]. For a temperature gradient of 0.1 C
over a 3-mm vertical distance inside the cell medium (3-mm
medium height corresponds to the suggested sample volume of
3 mL for the Petri dishes), the value of the product is still approximately 11 times lower than the value required for the initiation
of mass convection.
D. Exposure and Environmental Control
A high level of exposure and environmental control was realized. The feedback regulated exposure provides a low variability of SAR for the monolayer configuration (5.1%). Low
variability is also present for the suspension exposure (5.9%),
but only when water evaporation in the 60-mm Petri dish can
be excluded. This can be achieved by using a high-humidity incubator environment or a cover for the 60-mm dish. If water
evaporation is present, average variations of SAR are estimated
to be in the order of 16% (Table VI). With respect to the environmental control, it is a great advantage of the presented setup
that the exposure and sham units can be placed within the same
commercial incubator providing the environmental conditions.
The forced airflow exchange system allows excellent temperaC between two unexposed
ture control with differences
waveguides.
VI. CONCLUSION
An exposure system for conducting in vitro laboratory
studies in several European research institutes was realized
and characterized. The waveguide-based computer-controlled
setup enables the exposure of cell monolayers and suspensions
with an excellent SAR efficiency 50 and 10 (W/kg)/W,
respectively. The flexible signal unit allows the generation and
control of complex modulated signals, e.g., temporal changes
between different GSM operation modes (DTX/non-DTX).
The exposure field strength and environmental parameters
(air temperature, fan system) are continuously monitored.
The field information is used for feedback control. A coupled
electrothermal FDTD analysis was performed and resulted in a
nonuniformity of SAR of 30% and 40%. The temperature rise
was assessed by measurement and simulation, and a maximum
rise of 0.03 C/(W/kg) and 0.13 C/(W/kg) for monolayer
and suspension was found. No localized temperature “hot
spots” are generated within the cell medium. All simulations
were verified by dosimetric measurements.
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IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004
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Jürgen Schuderer was born in 1972. He received
the M.S. degree in physics from the University
of Freiburg, Freiburg, Germany, in 1999, and the
Ph.D. degree from the Swiss Federal Institute of
Technology (ETH), Zürich, Switzerland, in 2003.
He was with the Fraunhofer Institute for Physical
Measurement Techniques, Freiburg, Germany, where
he developed a fluoroptic sensor system to monitor
bioaffinity reactions. In late 1999, he joined the Integrated Systems Laboratory, ETH, where he was involved with the development of in vitro and humanexposure setups for risk-assessment studies, as well as with the development
of miniaturized dosimetric sensors. In 2003, he joined the Foundation for Research on Information Technologies in Society (IT’IS), Zürich, Switzerland. His
research interest is currently focused on RF dosimetry, biomedical sensors, and
computational electrodynamics.
Theodoros Samaras (S’93–A’97–M’02) was born
in 1968. He received the Physics degree from the
Aristotle University of Thessaloniki, Thessaloniki,
Greece, in 1990, the M.Sc. degree in medical
physics (with distinction) from the University of
Surrey, Surrey, U.K., in 1991, and the Ph.D. degree
in hyperthermia from the Aristotle University of
Thessaloniki, in 1996.
Following his military service, he joined the Federal Institute of Technology (ETH), Zürich, Switzerland, where he was involved with the modeling of the
interaction of electromagnetic waves with biological tissues. Since December
1999 he has been working in the Department of Physics of the Aristotle University of Thessaloniki as a Lecturer. His research interests include computational
electromagnetics, microwave applications, and biomedical engineering.
Dr. Samaras is a member of the European Society for Hyperthermic Oncology
(ESHO). In February 1999, he was the recipient of a Marie-Curie Fellowship
presented by the European Commission to work on the enhancement of superficial hyperthermia in the Hyperthermia Section, University Hospital Rotterdam-Daniel.
Walter Oesch was born in 1974. He received the
M.S. degree in geophysics from the Swiss Federal
Institute of Technology (ETH), Zürich, Switzerland,
in 2000 .
He then joined the Foundation for Research on
Information Technologies in Society (IT’IS), Zürich,
Switzerland. He specified, planned, designed,
and implemented the controlling and monitoring
software for various in vivo and in vitro exposure
setups. His primary research interest is concentrated
in the area of technical software engineering.
Denis Spät was born in 1976. He received the M.S.
degree in industrial engineering from the Technical
University of Darmstadt, Darmstadt, Germany, in
2003.
Since 2002, he has been a Scientific Assistant with
the Foundation for Research on Information Technologies in Society (IT’IS), Zürich, Switzerland. His
main research interest is RF dosimetry for bioexperiments focusing on the health-risk assessment of electromagnetic-field exposures.
Niels Kuster (M’93) was born in Olten, Switzerland,
in 1957. He received the M.S. and Ph.D. degrees in
electrical engineering from the Swiss Federal Institute of Technology (ETH), Zürich, Switzerland.
In 1993, he became a Professor with the Department of Electrical Engineering, ETH. In 1992, he
was an Invited Professor with the Electromagnetics
Laboratory, Motorola Inc., Fort Lauderdale, FL,
and in 1998, with the Metropolitan University of
Tokyo, Tokyo, Japan. In 1999 he became Director
of the Foundation for Research on Information
Technologies in Society (IT’IS), Zürich, Switzerland. His research interest is
currently focused on the area of reliable on/in-body wireless communications
and related topics. This includes measurement technology and computational
electrodynamics for evaluation of close near-fields in complex environments,
safe and reliable wireless communication links within the body or between
implanted devices and the outside for biometrics applications, development of
exposure setups and quality control for bioexperiments evaluating interaction
mechanisms, therapeutic effects, as well as potential health risks, and exposure
assessments.
Dr. Kuster is a member of several standardization bodies and has consulted
several government agencies on the issue of the safety of mobile communications. He also served on the boards of scientific societies, research management
councils for governments, and editorial boards.