In vitro exposure systems for RF exposures at 900 MHz

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IEEE TRANSACTIONS ON MICROWAVE THEORY ANDTECHNIQUES, VOL. 52, NO. 8, AUGUST 2004 2067 In Vitro Exposure Systems for RF Exposures at 900 MHz Jürgen Schuderer, Denis Spät, Theodoros Samaras, Member, IEEE, Walter Oesch, and Niels Kuster, Member, IEEE Abstract—In the context of European research programs, a ref- erence setup based on waveguides (WGs) has been developed for the conduct of standardized in vitro experiments at the mobile fre- quency bands of 835 and 935 MHz. Its performance is compared to those apparatus that are widely applied to expose cells settled as a monolayer on the bottom of a Petri dish, as well as for cells cultivated in homogenous suspension. The key figures-of-merit are uniformity of the specific absorption rate (SAR), induced temper- ature rise, SAR and volume efficiency, as well as the ability to en- sure tight exposure and environmental control. For the exposure of cell monolayers, the WG setup with Petri dishes in the -field maximum is superior in all respects. Reasonable performance is achieved with the resonator and transverse electromagnetic (TEM) cell. The best performance for cell suspensions is provided by the TEM cell for flasks in -polarization. Acceptable performance is also achieved with the WG system and resonator. The temperature rise is an issue of concern for all setups. Measures to suitably con- trol the temperature rise and to maintain equal temperature pro- files between exposure and sham have been implemented for the WG and TEM cell setups. Localized temperature “hot spots” in the cell medium can be excluded for all investigated systems. Index Terms—Dosimetry, exposure setup, RF, specific absorption rate (SAR). I. INTRODUCTION T HE assessment of the health risk posed by RF electro- magnetic field (EMF) exposures will be based mainly on epidemiological studies supported by in vivo results. In vitro studies are faster and cheaper, but of less direct relevance to human health. Nevertheless, they are fundamental for detecting possible risk factors, as well as sites and mechanisms of inter- actions. Although in vitro experiments can be replicated with less effort than in vivo or epidemiological studies, unsatisfac- tory and conflicting results have emerged from these studies. In many cases, the contradictions could not be resolved since the exposure parameters regarding detailed exposure character- ization, dosimetry, and thermal loads or hot spots were insuffi- ciently described. It is obvious that well-characterized exposure including a comprehensive analysis of possible artifacts is a pre- requisite for the interpretation and repeatability of experiments. The minimum requirements have been described in [4]. Manuscript received October 15, 2003; revised March 31, 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, D. Spät, W. Oesch, 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.2004.832010 The task to uniformly expose a few centiliters of cell medium at the level of occupational exposure has always been underes- timated. Some authors used the incident field levels as exposure merit and neglected that the coupling mechanism to Petri dishes is fundamentally different than that for human exposure and strongly depends upon the polarization of the incident fields, flask, amount of medium, location of the flask with respect to the exposure chamber and effects of the medium on the incident field [1], [2], [12]. Also underestimated was the meniscus [14] and the temperature rise induced by the energy absorption. Tight temperature control is not possible without active cooling, even for exposure levels as low as 1 W/kg. An exception is the exposure of cell monolayers inside Petri dishes by -polarization [1], [13]. This setup results in the most uniform cell exposure and in a low-temperature rise [15], en- abling the exposure of cells to levels above 2 W/kg with air cooling only. Schönborn et al. [12] presented a qualitative comparison be- tween the main concepts of setups, including the TEM cell, RF chamber, radial transmission line, waveguide (WG), and wire-patch (WP) cell. The purpose of this study was to conduct a quantitative comparison between exposure setups operating in the 900-MHz region. The reference setup presented here is a newly developed exposure unit based on WG setups. The perfor- mance is compared to an enhanced WP cell originally presented by Laval et al. [5], a transverse electromagnetic (TEM) cell uti- lizing -polarization [8], and the resonator with water cooling developed by Toivo et al. [16] for -polarization. The perfor- mance parameters of the first three setups have been analyzed by the methodology described hereafter. The values for the res- onator setup were derived from the literature as far as available. II. PERFORMANCE PARAMETERS The setups were compared with respect to the following per- formance parameters. Uniformity of SAR: The SAR distribution over the entire volume of cells should be as uniform as possible. Temperature Rise: Any in vitro experiments focusing on nonthermal effects should be performed without signif- icant temperature rise ( 0.1 C) for the exposed cells. Therefore, the maximum temperature increase together with its spatial distribution was analyzed. SAR Efficiency: The SAR efficiency describes the ratio between the average SAR for the cells and the input power at the feed of the exposure system. Low efficiency is often a reason for high costs because a high-power amplifier is required. 0018-9480/04$20.00 © 2004 IEEE

Transcript of In vitro exposure systems for RF exposures at 900 MHz

IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004 2067

In Vitro Exposure Systems for RFExposures at 900 MHz

Jürgen Schuderer, Denis Spät, Theodoros Samaras, Member, IEEE, Walter Oesch, and Niels Kuster, Member, IEEE

Abstract—In the context of European research programs, a ref-erence setup based on waveguides (WGs) has been developed forthe conduct of standardized in vitro experiments at the mobile fre-quency bands of 835 and 935 MHz. Its performance is comparedto those apparatus that are widely applied to expose cells settledas a monolayer on the bottom of a Petri dish, as well as for cellscultivated in homogenous suspension. The key figures-of-merit areuniformity of the specific absorption rate (SAR), induced temper-ature rise, SAR and volume efficiency, as well as the ability to en-sure tight exposure and environmental control. For the exposureof cell monolayers, the WG setup with Petri dishes in the -fieldmaximum is superior in all respects. Reasonable performance isachieved with the resonator and transverse electromagnetic (TEM)cell. The best performance for cell suspensions is provided by theTEM cell for flasks in -polarization. Acceptable performance isalso achieved with the WG system and resonator. The temperaturerise is an issue of concern for all setups. Measures to suitably con-trol the temperature rise and to maintain equal temperature pro-files between exposure and sham have been implemented for theWG and TEM cell setups. Localized temperature “hot spots” inthe cell medium can be excluded for all investigated systems.

Index Terms—Dosimetry, exposure setup, RF, specificabsorption rate (SAR).

I. INTRODUCTION

THE assessment of the health risk posed by RF electro-magnetic field (EMF) exposures will be based mainly on

epidemiological studies supported by in vivo results. In vitrostudies are faster and cheaper, but of less direct relevance tohuman health. Nevertheless, they are fundamental for detectingpossible risk factors, as well as sites and mechanisms of inter-actions. Although in vitro experiments can be replicated withless effort than in vivo or epidemiological studies, unsatisfac-tory and conflicting results have emerged from these studies.In many cases, the contradictions could not be resolved sincethe exposure parameters regarding detailed exposure character-ization, dosimetry, and thermal loads or hot spots were insuffi-ciently described. It is obvious that well-characterized exposureincluding a comprehensive analysis of possible artifacts is a pre-requisite for the interpretation and repeatability of experiments.The minimum requirements have been described in [4].

Manuscript received October 15, 2003; revised March 31, 2004. This workwas supported by the Swiss Agency of Education and Science, by the MobileManufacturers Forum, by the GSM Association, and by Sunrise TDC.

J. Schuderer, D. Spät, W. Oesch, and N. Kuster are with the Foundationfor Research on Information, Technologies in Society, Integrated SystemsLaboratory, Swiss Federal Institute of Technology, CH-8092 Zürich,Switzerland (e-mail: [email protected]).

T. Samaras is with the Department of Physics, Aristotle University ofThessaloniki, 54124 Thessaloniki, Greece.

Digital Object Identifier 10.1109/TMTT.2004.832010

The task to uniformly expose a few centiliters of cell mediumat the level of occupational exposure has always been underes-timated. Some authors used the incident field levels as exposuremerit and neglected that the coupling mechanism to Petri dishesis fundamentally different than that for human exposure andstrongly depends upon the polarization of the incident fields,flask, amount of medium, location of the flask with respect tothe exposure chamber and effects of the medium on the incidentfield [1], [2], [12]. Also underestimated was the meniscus [14]and the temperature rise induced by the energy absorption. Tighttemperature control is not possible without active cooling, evenfor exposure levels as low as 1 W/kg.

An exception is the exposure of cell monolayers inside Petridishes by -polarization [1], [13]. This setup results in the mostuniform cell exposure and in a low-temperature rise [15], en-abling the exposure of cells to levels above 2 W/kg with aircooling only.

Schönborn et al. [12] presented a qualitative comparison be-tween the main concepts of setups, including the TEM cell,RF chamber, radial transmission line, waveguide (WG), andwire-patch (WP) cell. The purpose of this study was to conducta quantitative comparison between exposure setups operatingin the 900-MHz region. The reference setup presented here is anewly developed exposure unit based on WG setups. The perfor-mance is compared to an enhanced WP cell originally presentedby Laval et al. [5], a transverse electromagnetic (TEM) cell uti-lizing -polarization [8], and the resonator with water coolingdeveloped by Toivo et al. [16] for -polarization. The perfor-mance parameters of the first three setups have been analyzedby the methodology described hereafter. The values for the res-onator setup were derived from the literature as far as available.

II. PERFORMANCE PARAMETERS

The setups were compared with respect to the following per-formance parameters.

• Uniformity of SAR: The SAR distribution over the entirevolume of cells should be as uniform as possible.

• Temperature Rise: Any in vitro experiments focusing onnonthermal effects should be performed without signif-icant temperature rise ( 0.1 C) for the exposed cells.Therefore, the maximum temperature increase togetherwith its spatial distribution was analyzed.

• SAR Efficiency: The SAR efficiency describes the ratiobetween the average SAR for the cells and the input powerat the feed of the exposure system. Low efficiency is oftena reason for high costs because a high-power amplifier isrequired.

0018-9480/04$20.00 © 2004 IEEE

2068 IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004

Fig. 1. Geometry and functional parts of the sXc900 WG setup. The total setupdimensions are 540� 500� 580 mm (height�width� depth). Distances ofdishes to short and WG center are given in Table I.

• Volume Efficiency: The volume efficiency describes theratio between the sample area (for cell monolayer) orvolume (for cell suspension) versus the space require-ments for the entire exposure unit. The volume is an issuesince if the volume efficiency is poor then the setup cannotbe used within an incubator, which would increase theeffort for environmental control. For a required samplevolume and area of 20 mL and 100 cm , the volumeefficiency should be more than 0.1 mL/L and 0.5 cm /L,respectively, to allow installation of the setup inside acommercial 200-L incubator.

• Provision of Exposure and Environmental Control:The quality of experimental data depends on the docu-mentation of the conditions during the experiment. StableRF exposure of cells depends on numerous details, whichare difficult to keep well controlled, e.g., amplifier drift,frequency drift, mechanical changes of RF cables, con-nectors and couplers, location of the flasks with respect tothe exposure unit, changes of the dielectric properties ofthe medium, amount of medium, changes in the meniscusprofile, and many more. Therefore, well-defined mechan-ical properties of the exposure chamber and continuousmonitoring of exposure conditions are a prerequisitefor high-quality experiments. Additionally, identicalenvironmental parameters for exposure and sham must beensured, e.g., temperature differences between exposureand sham should be less than 0.1 C.

III. EXPOSURE SYSTEMS

A. WG Setup sXc900

The WG setup sXc900 (sXc systems for eXposure of cells)is an adaptation of the sXc1800 system described in [15]. Itwas originally developed for cell-monolayer exposures and waslater extended for the exposure of cells in suspension. The setupis based on two rectangular R9 WGs, in which only the basic

mode can propagate for the frequency bands of interest,i.e., 800–950 MHz. The dimensions are given in Fig. 1. In orderto guarantee the same environmental conditions (temperature,humidity, CO /O ) for the exposed and sham cells, both WGs

Fig. 2. Dish holders for sXc900. 35-mm-diameter Petri dishes are used formonolayer exposure. 35-mm dishes placed inside 60-mm dishes filled withdistilled water are applied for suspension exposure.

TABLE IPOSITION OF THE PETRI DISHES INSIDE THE R9 WG WITH INNER DIMENSIONS

OF 125� 250� 520 mm (HEIGHT�WIDTH�LENGTH)

are placed inside the same incubator and a common location forthe air inlet was realized. The latter is necessary since incubatorscan have a large temperature profile of several tenths of a degree.

In contrast to the narrow-band cavity of the sXc1800,broad-band coax-to-WG adapters combined with three-stubtuners (1878B, Maury Microwave Cooperation, Ontario, CA)were used to enable operation at 835 and 935 MHz. Con-sequently, the power efficiency of the setup is considerablylower than for sXc1800 due to the losses in the adapter, cables,and tuner. The larger cross section of the R9 WG allows theplacement of eight Petri dishes per field maximum compared toonly two dishes in the R18 WG. The Petri dishes are arrangedin two towers, each with four dishes (Fig. 2). Cell monolayersare exposed in the -field maximum and cell suspension in the

-field maximum.The system was optimized and the dosimetry provided for the

same Petri dish arrangements as for sXc1800 as follows.

• Cell monolayers: 35-mm Petri dishes (33-mm effectiveinner diameter) filled with 2.2–4.9 mL of Dulbecco’sModified Eagle’s Medium (DMEM).

• Cell suspensions: Petri dishes exposed in -polarizationprovide higher uniformity of exposure when placed in alarge Petri dish filled with water or medium due to thestrong coupling at the sides of the dishes [5]. The setupwas optimized for 3.1-mL DMEM in the inner 35-mmPetri dish and 4.9-mL distilled water in the outer 60-mmPetri dish (54-mm effective inner diameter).

As for sXc1800, tight exposure and environmental controlwas realized using field sensors, temperature sensors for the airenvironment, and an optimized airflow system. The cooling ef-fectivity was enhanced by two strong fans per WG (4212NGN,Papst, Georgen, Germany: airflow 165 m /h) combined withtwo side plates at the dish holder to channel the airflow to the

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TABLE IIMATERIAL PARAMETERS USED IN THE SIMULATION (" : RELATIVE PERMITTIVITY, �: ELECTRIC CONDUCTIVITY,

c: SPECIFIC HEAT CAPACITY, k: THERMAL CONDUCTIVITY, �: MASS DENSITY)

area of the Petri dishes. The distances of the dishes to the shortand WG center are given in Table I.

The field sensor is based on a loop antenna (4-mm diam-eter) located in the center of the short ( -field maximumindependent of frequency). The signal unit of the WG setupis described in [15]. It provides flexible modulation schemes(global system for mobile communications (GSM) talk/dis-continuous transmission (DTX), digital advanced mobilephone service (DAMPS), etc.), continuous field control, andregulation (0.1-Hz update rate) and allows blinded protocolswith high data security.

B. WP Cell

The WP cell is an open radiating setup operated at 900 MHz.Its compact design is based on a 150 mm 150 mm parallel-plate configuration (29-mm distance) short circuited at the edgesby four plots [5]. Eight 35-mm Petri dishes (each placed insidea 60-mm dish with distilled water) are arranged symmetricallyaround the central coaxial feed. Since the WP cell is an opensetup, exposure and sham groups need to be placed in two dif-ferent incubators. The system in the investigated configurationhas no fan or other cooling. For the purpose of this study, theoriginal system was enhanced by: 1) distance keepers for thePetri dishes; 2) optimized Petri dish loading (to reduce the tem-perature rise, distilled water instead of cell medium is used forthe 60-mm dish); 3) -field sensors for monitoring and regula-tion; and 4) a computer-controlled signal unit, allowing blindedexposure protocols [15].

Research activities to overcome the low sham isolation andthe high temperature rise of the WP cell were recently presentedby Pinto et al. [9]. Systems for the exposure of four Petri dishesat 900 and 1800 MHz were developed. Shielding is realized withmetallic grids that isolate two independent WP systems placedwithin the same incubator. Contact cooling of the dish bottomsis applied by water cooling of the ground plate.

C. TEM Cell

Schönborn et al. [12] have shown that reasonable uniformexposures (SD: 40%) can also be achieved with -polar-ization. Nikoloski et al. [6] presented an elaborated setupbased on commercial TEM cells, which was evaluated for theexposure of cell suspensions at 835 MHz. The setup consistsof two modified TEM cells (IFI 110, Instruments for IndustryInc., Ronkonkoma, NY) that fit inside an incubator. T25 flasks(25 cm ) filled with 5 mL of DMEM medium are used. Anairflow system for cooling and fast atmospheric exchange isapplied. A signal unit similar to that of the sXc setups enables

TABLE IIINUMERICALLY APPLIED HEAT-TRANSFER COEFFICIENTS FOR MODELING

OF THERMAL BOUNDARIES. MODELS FOR WG SETUP MONOLAYER

EXPOSURES (Ml.), SUSPENSION EXPOSURES (Su.), AND

FOR THE WP CELL WERE ANALYZED

monitoring and blinded protocols. In the context of this study,the performance of the setup for cell monolayers has beenevaluated in addition to the data presented in [6].

D. Resonator Setup

The resonator setup consists of a short-circuited WG chamberat 900 MHz [16]. Four 60-mm-diameter Petri dishes are exposedin a standing-wave -field maximum in -polarization. Thedishes are placed on a glass plate, which is water cooled frombelow. In this way, a temperature stability of 0.3 C over therange from 0- to 10-W/kg average SAR is achieved [16]. Thesetup is operated outside of an incubator, whereby an airflowsystem connects the exposure area and incubator atmosphere.A monopole sensor is used to monitor the incident fields. Thesetup in the current state does not allow for blinded exposureprotocols.

IV. METHODS

A. Numerical Characterization

Similar dosimetric methods as described in [15] have beenapplied to characterize the exposure conditions for the WGsetup, WP cell and TEM cell. The performance parametersfor the resonator setup were derived from the literature but arenot complete. A numerical electrothermal FDTD analysis wasperformed with the simulation platform SEMCAD (SPEAG,Zürich, Switzerland). The numerical models, with a voxelresolution of 0.4 mm, contained meniscus profiles for all liquidsurfaces. Menisci were modeled according to the functionsgiven in [14]. The material parameters used in the simulationare listed in Table II. The dielectric properties were derivedfrom measurements at 37 C; the thermal properties were takenfrom [11].

Several medium volumes in the range from 2.2 to 4.9 mL(2–5-mm liquid height) were simulated for the monolayer ex-posure of the WG setup. A vertical extrapolation of the spe-cific absorption rate (SAR) to the cell monolayer was applied

2070 IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004

TABLE IVPERFORMANCE SUMMARY FOR CELL-MONOLAYER EXPOSURES WITH WG SETUP, WP CELL, TEM CELL, AND RESONATOR

TABLE VPERFORMANCE SUMMARY FOR CELL-SUSPENSION EXPOSURES WITH WG SETUP, WP CELL, TEM CELL, AND RESONATOR

[15]. For the suspension exposure in the WG setup, WP cell, andTEM cell, only one geometry was analyzed (WG setup and WPcell: 3 0.2 mL DMEM and 5 0.2 mL distilled water; TEMcell: 5-mL DMEM). Monolayer SAR values for the WP cell andTEM cell were derived by averaging all voxels from the lowestmedium layers ( mm). For suspension exposures, theSAR was evaluated: 1) for the entire medium; 2) for the mediumexcluding the meniscus; and 3) for the meniscus only. Finite-dif-ference time-domain (FDTD) corner voxels at the curved dishmedia interfaces of the Petri dishes were not considered for allSAR evaluations because they are sensitive to numerical stair-

casing artifacts. The total amount of neglected medium is lessthan 0.1 mL.

The temperature distribution was analyzed for a numericalmodel consisting of only one Petri dish or flask. A standing-wavefield exposure at 900 MHz was applied by two incident planewaves resulting in a similar SAR distribution as for the WG andWP setups. Heat transfer due to conduction, radiation, naturalconvection, and forced convection was considered with thesame methods as described in [15] (a flat plate approximation[3] of the cell medium was applied to assess the heat-transfercoefficients). The combined heat-transfer coefficients for the

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Fig. 3. SAR distribution for cell-monolayer exposure with the WG setup at835 MHz. (a) Vertical planes in the dish center for three medium volumes areshown for an incident H-field of 1.1 A/m. (b) Lowest horizontal plane in themedium (z = 0:2mm) is shown on a logarithmic scale for the two upper dishes.

thermal boundary modeling are given in Table III. Note that,due to the missing air cooling of the WP cell, much lessheat transfer via the dish and water interfaces is present. Heattransfer due to mass or fluid convection is unlikely [15] and wasnot considered. The simulations were validated by single-pointtemperature measurements (see below).

B. Experimental Verification

The experimental evaluation was performed with the DASY3near-field scanner (SPEAG) equipped with free space and dosi-metric probes. A 1-mm-diameter -field probe [10] was usedto map a vertical line in the center of the cell media (WG setupmonolayer: 4.9-mL DMEM, WG setup suspension and WP cell:3.1 0.1 mL DMEM).

The temperature rise was determined with resistive ther-mistor probes [15]. The data for the temperature response ofthe medium was used for: 1) determination of the local SAR byevaluation of the first 50 s of exposure; 2) determination of thetemperature rise at steady state; and 3) validation and optimiza-tion of the numerical simulations (heat-transfer coefficients forconvection were adjusted to fit the measurement data).

V. RESULTS

A. Performance Summary

The results for the performance of the investigated exposuresystems are shown in Table IV for the cell monolayer and inTable V for cell-suspension exposures. Quantitative data for thenonuniformity of the SAR distribution, temperature rise, SARefficiency, and volume efficiency are given. Experimental andenvironmental control is qualitatively evaluated. Fig. 3 showsthe SAR distribution for the monolayer exposure of the WGsetup. Vertical planes in the center of the Petri dish are shownfor three liquid volumes [see Fig. 3(a)]. The amount of mediuminserted must be carefully controlled since the SAR strongly de-pends upon the medium height. Most of the monolayer areais within a 2-dB radius from the maximum SAR value [seeFig. 3(a)]. The cell medium internal - and -field are perpen-

Fig. 4. SAR distribution for the WG setup for cell-suspension exposure (at835 MHz) and for the WP cell (at 900 MHz). A vertical plane in the dish centeris shown.

dicular to each other and polarized in the plane of the monolayer.The field impedance is low.

The exposure of cells in suspension with the WG setup andthe WP cell result in similar SAR distributions (Fig. 4). SARvalues are 4–5 times higher in the meniscus than for the restof the medium (Table V). Uniformity of the SAR is consider-ably enhanced if the cells are not located in the meniscus area.Therefore, the sedimentation behavior of the cells must be ana-lyzed. Exposure should be started after a sufficient time periodin which the cells have settled from the meniscus. In contrast tothe monolayer exposure, the internal -field is polarized per-pendicular to the medium surface, whereas the -field is par-allel. The field impedance is also low.

Fig. 5 and 6 show the simulated SAR and steady-state tem-perature distributions for the single dish models. Temperaturebecomes distributed without areas of localized “hot spots” forall setups. It can be seen that the temperature probe was placedinside the temperature maximum for the WG setup in mono-layer exposure (Fig. 5), but neither for the cell-suspension con-figuration, nor the WP cell (Fig. 6). Therefore, the measuredtemperature rise values in Table V were multiplied by the sim-ulated ratio of maximum to sensor value: 1.3 (WG setup), 1.1(WP cell), 1.1 (TEM cell). Detailed dosimetry data for the WGsetup at 835 and 935 MHz and for different cell medium vol-umes are given in Table VI.

B. Uncertainties and SAR Verification

The uncertainty for the SAR assessment and the SAR vari-ability were evaluated according to [7]. Normal or rectangularerror distributions were assumed in order to derive an estimatedstandard deviation for each uncertainty and variability contribu-tion. Table VII summarizes the investigated parameters for theuncertainty of the SAR assessment of the WG setup and WP cell(for the TEM cell, refer to [6]). Also given in this table are thedeviations between the SAR measurements and simulation. Forthe WG setup, an average deviation of 15% for the cell-mono-layer configuration and 17%/8% for -field/temperature evalu-ations in suspension were found. The corresponding deviationsfor the WP cell are 25%/7%, respectively.

2072 IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004

Fig. 5. Simulated SAR and steady-state temperature distribution for thesingle dish model at 900 MHz for monolayer exposure of the WG setup (starttemperature: 37 C). The same SAR values as for the measurement are used inthe simulation. The location of the temperature probe used for the experimentalassessment is indicated in this figure.

Fig. 7 shows the data for the -field measured SAR valuesof the WG setup (SAR was evaluated in the two upper dishes).While good agreement was achieved for the cell-monolayerconfiguration, boundary and immersion depth errors are presentfor suspension and WP cell measurements. The difficultiesarise from the geometrical configuration, whereby the fieldprobe needs to be positioned parallel to the incident as well asthe induced -fields. This leads to: 1) field enhancements whenthe probe tip comes close to the dish bottom; 2) immersiondepth errors when the tip comes close to the medium top; and3) coupling and scattering at the holes that were milled inorder to position the probes. Nevertheless, measurement andsimulation come close to each other in the area of the mediumcenter, which is free of artifacts.

The deviations between simulation and measurement are inthe range of the combined uncertainty for the SAR assessment(Table VII): WG setup (Ml.): 15% versus 20%, WG setup (Su.):17% versus 21%, WP cell: 25% versus 21%. Therefore, themeasured results can be regarded as a verification of the nu-merical techniques and support the reliability of the dosimetry.The exposure variability is summarized in Table VIII and is setin relation to the nonuniformity of the SAR distribution. For allsetups, the variability of SAR does not dominate the intrinsicvariability caused by the nonuniform SAR distribution.

VI. DISCUSSION

A. Cell-Monolayer Exposure

The WG setup provides the best performance for cell mono-layers. High uniformity of the SAR (deviations: 20%) together

Fig. 6. Simulated SAR and steady-state temperature distribution for the singledish model at 900 MHz for the WG setup suspension exposure and for the WPcell. The same average SAR values (without meniscus evaluation) as for themeasurement are used in the simulation (WG setup: 7.8 W/kg, WP cell: 4.6W/kg). The start temperature of thermal simulation was 37 C. The location ofthe temperature probe used for the experimental assessment is indicated in thisfigure.

with a low temperature rise C/(W/kg) is achieved(Table IV). Due to the characteristic SAR maximum at the dishboundary, air cooling is very efficient and allows exposure upto 5 W/kg without significant temperature load ( C).The efficiency could be greatly improved by internal tuning. Ad-ditionally, the WG setup fulfills all requirements for exposureand environmental control and low variability. Liquid cooling,based on an external medium at a different temperature, is notrequired. The same is true for the TEM cell, which also pro-vides reasonably good uniformity. Without active cooling, theWP cell can only be applied for exposures with SAR values upto 0.4 W/kg ( C). Liquid cooling has been intro-duced for the resonator and WP cell, thus overcoming some ofthese disadvantages. However, the potential engineering prob-lems to guarantee the same cooling effectivity, as well as thesame absolute temperature for the cells in sham and exposure,should not be underestimated. Passive systems are less suscep-tible to possible malfunctions. All systems have a comparableexposure area of approximately 100 cm , whereby the WP cellclearly provides the best volume efficiency.

B. Cell-Suspension Exposure

Uniform exposure of cells in suspension is an issue for allinvestigated systems. None of the examined setups fulfills therequirement of less than 30% deviation from uniformity of theSAR, as formulated in [4]. However, the TEM cell provides

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TABLE VIDETAILED DOSIMETRY FOR WG SETUP “sXc900”

TABLE VIIUNCERTAINTY ANALYSIS FOR THE SAR ASSESSMENT OF WG SETUP MONOLAYER (Ml.), SUSPENSION (Su.), AND WP CELL

EXPOSURES. ESTIMATED STANDARD DEVIATIONS WERE DERIVED AND ARE COMPARED TO THE

DIFFERENCE BETWEEN MEASUREMENT AND SIMULATION

Fig. 7. SAR along the center of the medium for the two upper dishes (towers 1 and 2). E-field measured data is compared to FDTD simulations at 835 MHz forthe monolayer configuration (4.9-mL medium, 5-mm liquid height) and suspension configuration (3.1-mL medium, 3-mm liquid height) of the WG setup. z = 0

corresponds to the dish/medium interface.

2074 IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES, VOL. 52, NO. 8, AUGUST 2004

TABLE VIIISAR VARIABILITY ANALYSIS FOR WG SETUP MONOLAYER (Ml.), SUSPENSION (Su.), AND WP CELL EXPOSURES.

ESTIMATED STANDARD DEVIATIONS WERE DERIVED AND ARE COMPARED TO THE

NONUNIFORMITY OF THE SAR DISTRIBUTION

good exposure performance: nonuniformity of SAR: 46%, tem-perature rise: 0.05 C/(W/kg) and SAR efficiency: 6 (W/kg)/W(Table V). The necessary exposure and environmental controlis also provided. Reasonable performance is achieved withthe WG setup for the case of cells not in the meniscus; anonuniformity of 54% is present at a temperature rise of 0.12C/(W/kg) (Table V). Evaporation of distilled water in the

60-mm-diameter dish for WG and WP exposures represents asource of considerable SAR variation (Table VIII: 19%–26%).It can be compensated by using a high humidity incubatorenvironment or using a cover for the 60-mm dishes. High SARvalues up to 10 W/kg for cell suspensions can be achievedwith the resonator due to its water-cooling system. However,to quantify the resonator performance in detail, an evaluationof the uniformity of the exposure for cell medium modelswith meniscus profiles is required. The resonator should beupgraded to allow blinded protocols, e.g., by using a pair ofresonators with blinded cooling of the exposure group. Forcell suspension, the WP cell without cooling also cannot berecommended. The exposure volume of approximately 20 mLis comparable for all systems with the best volume efficiencyfor the WP cell.

VII. CONCLUSION

In this paper, different in vitro exposure setups have beendosimetrically analyzed for their performance with respect touniformity of SAR, temperature rise, SAR efficiency, volumeefficiency, and exposure/environmental control. The investi-gated setups were the sXc900 WG setup, WP cell [5], TEM cellin -polarization [8], and a resonator setup with water cooling[16]. The analysis revealed that the WG system provides supe-rior performance for the exposure of cell monolayers. The keyparameters are the low nonuniformity of the SAR (20%) andthe low temperature rise for the cells [0.02 C(W/kg)], whileproviding full exposure and environmental control. Uniformityof the SAR is a fundamental issue for cell suspensions. Therequired nonuniformity of less than 30% [4] was not achievedby any of the setups. The best performance for cell suspensions

is given by the TEM cell with a nonuniformity of SAR of46% and a temperature rise of 0.05 C/(W/kg). The WP cellfor the investigated configuration without cooling cannot berecommended due to its high temperature rise. Water-cooledsystems, TEM cells, WP cells, and resonators must be carefullyanalyzed before utilization for in vitro experiments with highSAR exposures.

REFERENCES

[1] M. Burkhardt, K. Pokovic, M. Gnos, T. Schmid, and N. Kuster, “Numer-ical and experimental dosimetry of Petri dish exposure setups,” Bioelec-tromagnetics, vol. 17, pp. 483–493, 1996.

[2] A.-W. Guy, C.-K. Chou, and J.-A. McDugall, “A quarter century of invitro research: A new look at exposure methods,” Bioelectromagnetics,vol. 20, pp. 21–39, 1999.

[3] J.-P. Holman, Heat Transfer, 8th ed. Boston, MA: McGraw-Hill, 1997.[4] N. Kuster and F. Schönborn, “Recommended minimal requirements

and development guidelines for exposure setups of bio-experimentsaddressing the health risk concern of wireless communications,”Bioelectromagnetics, vol. 21, pp. 508–514, 2000.

[5] L. Laval, P. Leveque, and B. Jecko, “A new in vitro exposure device forthe mobile frequency of 900 MHz,” Bioelectromagnetics, vol. 21, pp.255–263, 2000.

[6] N. Nikoloski, J. Fröhlich, T. Samaras, J. Schuderer, and N. Kuster,“Dosimetric revaluation of the TEM cell setup for replication study,”Bioelectromagnetics, 2004, submitted for publication.

[7] “Guidelines for evaluating and expressing the uncertainty of NIST mea-surement results,” NIST, Gaithersburg, MD, Tech. Rep. Tn1297, 1994.

[8] M. Penafiel, T. Litovitz, D. Krause, A. Desta, and M. Mullins, “Roleof modulation on the effect of microwaves on ornithine decarboxylaseactivity in L929 cells,” Bioelectromagnetics, vol. 18, pp. 132–141, 1997.

[9] R. Pinto, S. Mancini, L. Ardoino, and G.-A. Lovisolo, “Controlledsetups for biological activities,” presented at the RF Interaction withHumans Conf., London, U.K., Feb. 2003.

[10] K. Pokovic, T. Schmid, and N. Kuster, “Millimeter-resolution E-fieldprobe for isotropic measurement in lossy media between 100 MHz and20 GHz,” IEEE Trans. Instrum. Meas., vol. 49, pp. 873–878, Aug. 2000.

[11] T. Samaras, P. Regli, and N. Kuster, “Electromagnetic and heat compu-tations for nonionizing radiation dosimetry,” Phys. Med. Biol., vol. 45,pp. 2233–2246, 2000.

[12] F. Schönborn, K. Pokovic, M. Burkhardt, and N. Kuster, “Basis for op-timization of in vitro exposure apparatus for health hazard evaluationsof mobile communications,” Bioelectromagnetics, vol. 22, pp. 547–559,2001.

[13] F. Schönborn, K. Pokovic, A. Wobus, and N. Kuster, “Design, optimiza-tion, realization and analysis of an in vitro system for the exposure ofembryonic stem cells at 1.71 GHz,” Bioelectromagnetics, vol. 21, pp.372–384, 2000.

SCHUDERER et al.: IN VITRO EXPOSURE SYSTEMS FOR RF EXPOSURES 2075

[14] J. Schuderer and N. Kuster, “The effect of the meniscus at the solid/liquidinterface on the SAR distribution in Petri dishes and flasks,” Bioelectro-magnetics, vol. 24, pp. 103–108, 2003.

[15] J. Schuderer, T. Samaras, W. Oesch, D. Spät, and N. Kuster, “High peakSAR exposure unit with tight exposure and environmental control for invitro experiments at 1800 MHz,” IEEE Trans. Microwave Theory Tech.,vol. 52, pp. 2057–2066, Aug. 2004.

[16] T. Toivo, A.-P. Sihvonen, L. Puranen, and K. Keskinen, “Water cooledwaveguide chambers for exposure of cells in vitro at 900 MHz,” in 5thInt. Congr. Eur. Bioelectromagnetics Association, Helsinki, Finland,2001, pp. 62–63.

Jürgen Schuderer was born in 1972. He receivedthe M.S. degree in physics from the Universityof Freiburg, Freiburg, Germany, in 1999, and thePh.D. degree from the Swiss Federal Institute ofTechnology (ETH), Zürich, Switzerland, in 2003.

He was with the Fraunhofer Institute for PhysicalMeasurement Techniques, Freiburg, Germany, wherehe developed a fluoroptic sensor system to monitorbioaffinity reactions. In late 1999, he joined the In-tegrated Systems Laboratory, ETH, where he was in-volved with the development of in vitro and human-

exposure setups for risk-assessment studies, as well as with the developmentof miniaturized dosimetric sensors. In 2003, he joined the Foundation for Re-search on Information Technologies in Society (IT’IS), Zürich, Switzerland. Hisresearch interest is currently focused on RF dosimetry, biomedical sensors, andcomputational electrodynamics.

Denis Spät was born in 1976. He received the M.S.degree in industrial engineering from the TechnicalUniversity of Darmstadt, Darmstadt, Germany, in2003.

Since 2002, he has been a Scientific Assistant withthe Foundation for Research on Information Tech-nologies in Society (IT’IS), Zürich, Switzerland. Hismain research interest is RF dosimetry for bioexperi-ments focusing on the health-risk assessment of elec-tromagnetic-field exposures.

Theodoros Samaras (S’93–A’97–M’02) was bornin 1968. He received the Physics degree from theAristotle University of Thessaloniki, Thessaloniki,Greece, in 1990, the M.Sc. degree in medicalphysics (with distinction) from the University ofSurrey, Surrey, U.K., in 1991, and the Ph.D. degreein hyperthermia from the Aristotle University ofThessaloniki, in 1996.

Following his military service, he joined the Fed-eral Institute of Technology (ETH), Zürich, Switzer-land, where he was involved with the modeling of the

interaction of electromagnetic waves with biological tissues. Since December1999 he has been working in the Department of Physics of the Aristotle Univer-sity of Thessaloniki as a Lecturer. His research interests include computationalelectromagnetics, 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 Fellowshippresented by the European Commission to work on the enhancement of su-perficial hyperthermia in the Hyperthermia Section, University Hospital Rot-terdam-Daniel.

Walter Oesch was born in 1974. He received theM.S. degree in geophysics from the Swiss FederalInstitute of Technology (ETH), Zürich, Switzerland,in 2000 .

He then joined the Foundation for Research onInformation Technologies in Society (IT’IS), Zürich,Switzerland. He specified, planned, designed,and implemented the controlling and monitoringsoftware for various in vivo and in vitro exposuresetups. His primary research interest is concentratedin the area of technical software engineering.

Niels Kuster (M’93) was born in Olten, Switzerland,in 1957. He received the M.S. and Ph.D. degrees inelectrical engineering from the Swiss Federal Insti-tute of Technology (ETH), Zürich, Switzerland.

In 1993, he became a Professor with the Depart-ment of Electrical Engineering, ETH. In 1992, hewas an Invited Professor with the ElectromagneticsLaboratory, Motorola Inc., Fort Lauderdale, FL,and in 1998, with the Metropolitan University ofTokyo, Tokyo, Japan. In 1999 he became Directorof the Foundation for Research on Information

Technologies in Society (IT’IS), Zürich, Switzerland. His research interest iscurrently focused on the area of reliable on/in-body wireless communicationsand related topics. This includes measurement technology and computationalelectrodynamics for evaluation of close near-fields in complex environments,safe and reliable wireless communication links within the body or betweenimplanted devices and the outside for biometrics applications, development ofexposure setups and quality control for bioexperiments evaluating interactionmechanisms, therapeutic effects, as well as potential health risks, and exposureassessments.

Dr. Kuster is a member of several standardization bodies and has consultedseveral government agencies on the issue of the safety of mobile communica-tions. He also served on the boards of scientific societies, research managementcouncils for governments, and editorial boards.