A Resonant System for In Vitro Studies Emulating Wireless Power Transfer Exposure at 13.56 MHz.

This paper presents the design of a resonant system for in vitro studies to emulate the exposure of a monolayer of cells to a wireless power transfer system operating at 13.56 MHz. The design procedure targets a system, which maximizes the specific absorption rate (SAR) uniformity on the plane where the layer is cultured, as well as SAR efficiency (defined as SAR over the input power), within the size constraints of a standard incubator. Three resonant wireless power transfer systems with different commonly used loop/coil geometries (cylindrical with circular and square cross-sections and annular) were compared with assess the configuration maximizing the considered design criteria. The system performance in terms of reflection and transmission coefficients, as well as generated E- and H-fields, was characterized numerically and experimentally inside the incubator. Moreover, SAR was computed at the monolayer level. The system equipped with cylindrical coils with square cross-sections led to a high electromagnetic field uniformity in in vitro biological samples. In particular, the uniformities in E and SAR at the layer level were within 7.9% and 5.5%, respectively. This was achieved with the variation in H below the usually considered ±5% limit. © 2020 Bioelectromagnetics Society.

Exposure Assessment in Millimeter-Wave Reverberation Chamber Using Murine Phantoms.

This study deals with the design and calibration of the first mode-stirred reverberation chamber (RC) in the 60-GHz-band adapted for in vivo bioelectromagnetic studies. In addition to the interface for electromagnetic and thermal dosimetry, the interfaces for lighting and ventilation were integrated into the RC walls while preserving acceptable shielding. The RC with mechanical and electronic steering capabilities is characterized in the 55-65 GHz range. To this end, murine skin-equivalent phantoms of realistic shape were designed and fabricated. Their complex permittivity is within ±12% of the target value of murine skin (6.19-j5.81 at 60 GHz). The quality factor of the RC loaded with an animal cage, bedding litter, and five murine phantoms was found to be 1.2 × 104 . The losses inside the RC were analyzed, and it was demonstrated that the main sources of the power dissipation were the phantoms and mice cage. The input power required to reach the average incident power density of 1 and 5 mW/cm2 was found to be 0.23 and 1.14 W, respectively. Surface heating of the mice models was measured in the infrared (IR) range using a specifically designed interface, transparent at IR and opaque at millimeter waves (mmW). Experimental results were compared with an analytical solution of the heat transfer equation and to full-wave computations. Analytical and numerical results were in very good agreement with measurements (the relative deviation after 90 min of exposure was within 4.2%). Finally, a parametric study was performed to assess the impact of the thermophysical parameters on the resulting heating. Bioelectromagnetics. 2020;41:121-135. © 2020 Bioelectromagnetics Society.

Optimal Radiation of Body-Implanted Capsules.

Autonomous implantable bioelectronics requires efficient radiating structures for data transfer and wireless powering. The radiation of body-implanted capsules is investigated to obtain the explicit radiation optima for E- and B-coupled sources of arbitrary dimensions and properties. The analysis uses the conservation-of-energy formulation within dispersive homogeneous and stratified canonical body models. The results reveal that the fundamental bounds exceed by far the efficiencies currently obtained by conventional designs. Finally, a practical realization of the optimal source based on a dielectric-loaded cylindrical-patch structure is presented. The radiation efficiency of the structure closely approaches the theoretical bounds and shows a fivefold improvement over existing systems.

Millimeter-Wave Heating in In Vitro Studies: Effect of Convection in Continuous and Pulse-Modulated Regimes.

Shallow penetration of millimeter waves (MMW) and non-uniform illumination in in vitro experiments result in a non-uniform distribution of the specific absorption rate (SAR). These SAR gradients trigger convective currents in liquids affecting transient and steady-state temperature distributions. We analyzed the effect of convection on temperature dynamics during MMW exposure in continuous-wave (CW) and pulsed-wave (PW) amplitude-modulated regimes using micro-thermocouples. Temperature rise kinetics are characterized by the occurrence of a temperature peak that shifts to shorter times as the SAR of the MMW exposure increases and precedes initiation of convection in bulk. Furthermore, we demonstrate that the liquid volume impacts convection. Increasing the volume results in earlier triggering of convection and in a greater cooling rate after the end of the exposure. In PW regimes, convection strongly depends on the pulse duration that affects the heat pulse amplitude and cooling rate. The latter results in a change of the average temperature in PW regime. Bioelectromagnetics. 2019;40:553-568. © 2019 Bioelectromagnetics Society.

Multifunctional Flexible Sensor Based on Laser-Induced Graphene.

The paper presents the design and fabrication of a low-cost and easy-to-fabricate laser-induced graphene sensor together with its implementation for multi-sensing applications. Laser-irradiation of commercial polymer film was applied for photo-thermal generation of graphene. The graphene patterned in an interdigitated shape was transferred onto Kapton sticky tape to form the electrodes of a capacitive sensor. The functionality of the sensor was validated by employing them in electrochemical and strain-sensing scenarios. Impedance spectroscopy was applied to investigate the response of the sensor. For the electrochemical sensing, different concentrations of sodium sulfate were prepared, and the fabricated sensor was used to detect the concentration differences. For the strain sensing, the sensor was deployed for monitoring of human joint movements and tactile sensing. The promising sensing results validating the applicability of the fabricated sensor for multiple sensing purposes are presented.

Untargeted Metabolomics Reveal Lipid Alterations upon 2-Deoxyglucose Treatment in Human HaCaT Keratinocytes.

The glucose analogue 2-deoxyglucose (2-DG) impedes cancer progression in animal models and is currently being assessed as an anticancer therapy, yet the mode of action of this drug of high clinical significance has not been fully delineated. In an attempt to better characterize its pharmacodynamics, an integrative UPLC-Q-Exactive-based joint metabolomic and lipidomic approach was undertaken to evaluate the metabolic perturbations induced by this drug in human HaCaT keratinocyte cells. R-XCMS data processing and subsequent multivariate pattern recognition, metabolites identification, and pathway analyses identified eight metabolites that were most significantly changed upon a 3 h 2-DG exposure. Most of these dysregulated features were emphasized in the course of lipidomic profiling and could be identified as ceramide and glucosylceramide derivatives, consistently with their involvement in cell death programming. Even though metabolomic analyses did not generally afford such clear-cut dysregulations, some alterations in phosphatidylcholine and phosphatidylethanolamine derivatives could be highlighted as well. Overall, these results support the adequacy of the proposed analytical workflow and might contribute to a better understanding of the mechanisms underlying the promising effects of 2-DG.

Microscale temperature and SAR measurements in cell monolayer models exposed to millimeter waves.

Due to shallow penetration of millimeter waves (MMW) and convection in liquid medium surrounding cells, the problem of accurate assessment of local MMW heating in in vitro experiments remains unsolved. Conventional dosimetric MMW techniques, such as infrared imaging or fiber optic (FO) sensors, face several inherent limits. Here we propose a methodology for accurate local temperature measurement and subsequent specific absorption rate (SAR) retrieval using microscale thermocouples (TC). SAR was retrieved by fitting the measured initial temperature rise to the numerical solution of an equivalent thermal model. It was found that the accuracy of temperature measurement depends on thermosensor size, that is, the smaller TC, the more accurate the temperature measurement. SAR determined using TC with lead diameters of 25 and 75 µm demonstrated 98.5% and 80.4% match with computed SAR, respectively. However, both TC provided the same temperature rises in long run (> 10 min). FO probe failed to measure adequately local heating both for short and long exposures due to the relatively large size of the probe sensor (400 µm) and time constant (0.6 s). Calculated SAR in the cell monolayer was almost two times lower than that in the surrounding liquid. It was shown that the impact of the cell monolayer on heating due to its small thickness (5 to 10 µm) can be considered as negligible. Moreover, we demonstrated the possibility of accurate measurement of MMW-induced thermal pulses (up to 10 °C) using 25 µm TC. Bioelectromagnetics. 38:11-21, 2017. © 2016 Wiley Periodicals, Inc.

Impact of 60-GHz millimeter waves on stress and pain-related protein expression in differentiating neuron-like cells.

Millimeter waves (MMW) will be increasingly used for future wireless telecommunications. Previous studies on skin keratinocytes showed that MMW could impact the mRNA expression of Transient Receptor Potential cation channel subfamily Vanilloid, member 2 (TRPV2). Here, we investigated the effect of MMW exposure on this marker, as well as on other membrane receptors such as Transient Receptor Potential cation channel subfamily Vanilloid, member 1 (TRPV1) and purinergic receptor P2X, ligand-gated ion channel, 3 (P2 × 3). We exposed the Neuroscreen-1 cell line (a PC12 subclone), in order to evaluate if acute MMW exposures could impact expression of these membrane receptors at the protein level. Proteotoxic stress-related chaperone protein Heat Shock Protein 70 (HSP70) expression level was also assessed. We used an original high-content screening approach, based on fluorescence microscopy, to allow cell-by-cell analysis and to detect any cell sub-population responding to exposure. Immunocytochemistry was done after 24 h MMW exposure of cells at 60.4 GHz, with an incident power density of 10 mW/cm(2) . Our results showed no impact of MMW exposure on protein expressions of HSP70, TRPV1, TRPV2, and P2 × 3. Moreover, no specific cell sub-populations were found to express one of the studied markers at a different level, compared to the rest of the cell populations. However, a slight insignificant increase in HSP70 expression and an increase in protein expression variability within cell population were observed in exposed cells, but controls showed that this was related to thermal effect. Bioelectromagnetics. 37:444-454, 2016. © 2016 Wiley Periodicals, Inc.

Millimeter waves as a source of selective heating of skin.

This study demonstrates that 20-100 GHz range can be used for spatially-accurate focusing of heating inside the skin achieved by varying frequency and exposure beam size, as well as by enforcing air convection. The latter is also used to reduce overheating of skin surface. Heating at different skin depths depending on these parameters is investigated in detail using the hybrid bio-heat equation. In particular, it is shown that decreasing frequency and/or increasing exposure beam size at forced airflow result in elevation of heating of deeper layers of tissue and decrease of skin surface temperature. Changes of water content within 15%, which exceed those due to aging and presence of tumors, only slightly affect heating. Exposure intensity necessary to reach a target temperature significantly increases in different areas of body with elevated blood flow. Dependence on exposure intensity and hyperthermia treatment duration is also investigated and discussed. Results of this study suggest that the lower part of the millimeter-wave range is an attractive alternative for non-invasive thermal treatment of skin cancer with a high spatial resolution.

Impact of 60-GHz millimeter waves and corresponding heat effect on endoplasmic reticulum stress sensor gene expression.

Emerging high data rate wireless communication systems, currently under development, will operate at millimeter waves (MMW) and specifically in the 60 GHz band for broadband short-range communications. The aim of this study was to investigate potential effects of MMW radiation on the cellular endoplasmic reticulum (ER) stress. Human skin cell lines were exposed at 60.4 GHz, with incident power densities (IPD) ranging between 1 and 20 mW/cm(2) . The upper IPD limits correspond to the ICNIRP local exposure limit for the general public. The expression of ER-stress sensors, namely BIP and ORP150, was then examined by real-time RT-PCR. Our experimental data demonstrated that MMW radiations do not change BIP or ORP150 mRNA basal levels, whatever the cell line, the exposure duration or the IPD level. Co-exposure to the well-known ER-stress inducer thapsigargin (TG) and MMW were then assessed. Our results show that MMW exposure at 20 mW/cm(2) inhibits TG-induced BIP and ORP150 over expression. Experimental controls showed that this inhibition is linked to the thermal effect resulting from the MMW exposure.

Transcriptional landscape of human keratinocyte models exposed to 60-GHz millimeter-waves.

The use of millimeter waves (MMW) will exponentially grow in the coming years due to their future utilization in 5G/6G networks. The question of possible biological effects at these frequencies has been raised. In this present study, we aimed to investigate gene expression changes under exposure to MMW using the Bulk RNA Barcoding and sequencing (BRB-seq) technology. To address this issue, three exposure scenarios were performed aiming at: i) comparing the cellular response of two primary culture of keratinocytes (HEK and NHEK) and one keratinocyte derivate cell line (HaCaT) exposed to MMW; ii) exploring the incident power density dose-effect on gene expression in HaCaT cell line; and, iii) studying the exposure duration at the new ICNIRP exposure limit for the general population. With the exception of heat effect induced by high power MMW (over 10 mW/cm2), those exposure scenarios have not enabled us to demonstrate important gene expression changes in the different cell populations studied. Very few differentially genes were observed between MMW exposed samples and heat shock control, and most of them were significantly associated with heat shock response that may reflect small differences in the heat generation. Together these results show that acute exposure to MMW has no effects on the transcriptional landscape of human keratinocyte models under athermal conditions.

Quasi-static approximation error of electric field analysis for transcranial current stimulation.

Objective.Numerical modeling of electric fields induced by transcranial alternating current stimulation (tACS) is currently a part of the standard procedure to predict and understand neural response. Quasi-static approximation (QSA) for electric field calculations is generally applied to reduce the computational cost. Here, we aimed to analyze and quantify the validity of the approximation over a broad frequency range.Approach.We performed electromagnetic modeling studies using an anatomical head model and considered approximations assuming either a purely ohmic medium (i.e. static formulation) or a lossy dielectric medium (QS formulation). The results were compared with the solution of Maxwell's equations in the cases of harmonic and pulsed signals. Finally, we analyzed the effect of electrode positioning on these errors.Main results.Our findings demonstrate that the QSA is valid and produces a relative error below 1% up to 1.43 MHz. The largest error is introduced in the static case, where the error is over 1% across the entire considered spectrum and as high as 20% in the brain at 10 Hz. We also highlight the special importance of considering the capacitive effect of tissues for pulsed waveforms, which prevents signal distortion induced by the purely ohmic approximation. At the neuron level, the results point a difference of sense electric field as high as 22% at focusing point, impacting pyramidal cells firing times.Significance.QSA remains valid in the frequency range currently used for tACS. However, neglecting permittivity (static formulation) introduces significant error for both harmonic and non-harmonic signals. It points out that reliable low frequency dielectric data are needed for accurate transcranial current stimulation numerical modeling.

Near-field dosimetry for in vitro exposure of human cells at 60 GHz.

Due to the expected mass deployment of millimeter-wave wireless technologies, thresholds of potential millimeter-wave-induced biological and health effects should be carefully assessed. The main purpose of this study is to propose, optimize, and characterize a near-field exposure configuration allowing illumination of cells in vitro at 60 GHz with power densities up to several tens of mW/cm(2) . Positioning of a tissue culture plate containing cells has been optimized in the near-field of a standard horn antenna operating at 60 GHz. The optimal position corresponds to the maximal mean-to-peak specific absorption rate (SAR) ratio over the cell monolayer, allowing the achievement of power densities up to 50 mW/cm(2) at least. Three complementary parameters have been determined and analyzed for the exposed cells, namely the power density, SAR, and temperature dynamics. The incident power density and SAR have been computed using the finite-difference time-domain (FDTD) method. The temperature dynamics at different locations inside the culture medium are measured and analyzed for various power densities. Local SAR, determined based on the initial rate of temperature rise, is in a good agreement with the computed SAR (maximal difference of 5%). For the optimized exposure setup configuration, 73% of cells are located within the ±3 dB region with respect to the average SAR. It is shown that under the considered exposure conditions, the maximal power density, local SAR, and temperature increments equal 57 mW/cm(2) , 1.4 kW/kg, and 6 °C, respectively, for the radiated power of 425 mW.

Complex permittivity of representative biological solutions in the 2-67 GHz range.

The main purpose of this study is to provide experimental data on the complex permittivity of some biological solutions in the 2-67 GHz range at room and human body temperatures. The permittivity measurements are performed using an open-ended coaxial probe. Permittivity spectra of several representative monomolecular solutions of proteins, amino acids, nucleic acids, and carbohydrates are analyzed and compared. Furthermore, measurements have also been performed for complex biomolecular solutions, including bovine serum albumin (BSA)-DNA-glucose mixture, culture medium, and yeast extract solution. The results demonstrate that for concentrations below 1%, the permittivity spectra of the solutions do not substantially differ from that of distilled water. Measurements carried out for 4% and 20% BSA solutions show that the presence of proteins results in a decrease in permittivity. For highly concentrated RNA solutions (3%), a slight increase in the imaginary part of the permittivity is observed below 10 GHz. Experimental data show that free water permittivity can be used for modeling of the culture medium above 10 GHz. However, at lower frequencies a substantial increase in the imaginary part of the permittivity due to ionic conductivity should be carefully taken into account. A similar increase has also been observed for the yeast extract solution in the lower frequency region of the considered spectrum. Above 10 GHz, the high concentration of proteins and other low-permittivity components of the yeast extract solution results in a decrease in the complex permittivity compared to that of water. Obtained data are of utmost importance for millimeter-wave dosimetry studies.

Whole-genome expression analysis in primary human keratinocyte cell cultures exposed to 60 GHz radiation.

The main purpose of this study is to investigate potential responses of skin cells to millimeter wave (MMW) radiation increasingly used in the wireless technologies. Primary human skin cells were exposed for 1, 6, or 24 h to 60.4 GHz with an average incident power density of 1.8 mW/cm(2) and an average specific absorption rate of 42.4 W/kg. A large-scale analysis was performed to determine whether these exposures could affect the gene expression. Gene expression microarrays containing over 41,000 unique human transcript probe sets were used, and data obtained for sham and exposed cells were compared. No significant difference in gene expression was observed when gene expression values were subjected to a stringent statistical analysis such as the Benjamini-Hochberg procedure. However, when a t-test was employed to analyze microarray data, 130 transcripts were found to be potentially modulated after exposure. To further quantitatively analyze these preselected transcripts, real-time PCR was performed on 24 genes with the best combination of high fold change and low P-value. Five of them, namely CRIP2, PLXND1, PTX3, SERPINF1, and TRPV2, were confirmed as differentially expressed after 6 h of exposure. To the best of our knowledge, this is the first large-scale study reporting on potential gene expression modification associated with MMW radiation used in wireless communication applications.

Millimeter-Wave Heating In Vitro: Local Microscale Temperature Measurements Correlated to Heat Shock Cellular Response.

OBJECTIVE: Cellular sensitivity to heat is highly variable depending on the cell line. The aim of this paper is to assess the cellular sensitivity of the A375 melanoma cell line to continuous (CW) millimeter-waves (MMW) induced heating at 58.4 GHz, between 37 °C and 47 °C to get a deeper insight into optimization of thermal treatment of superficial skin cancer. METHODS: Phosphorylation of heat shock protein 27 (HSP27) was mapped within an area of about 30 mm 2 to visualize the variation of heat-induced cellular stress as a function of the distance from the waveguide aperture (MMW radiation source). A multiphysics computational approach was then adopted to yield both electromagnetic and thermal field distributions as well as corresponding specific absorption rate (SAR) and temperature elevation. Induced temperature rise was experimentally measured using a micro-thermocouple ( µTC). RESULTS: Coupling of the incident electromagnetic (EM) field with µTC leads was first characterized, and optimal µTC placing was identified. HSP27 phosphorylation was induced at temperatures ≥ 41 °C, and its level increases as a function of the thermal dose delivered, remaining mostly focused within 3 mm 2. CONCLUSION: Phosphorylation of HSP27 represents a valuable marker of cellular stress of A375 melanoma cells under MMW exposure, providing both quantitative and spatial information about the distribution of the thermal stress. SIGNIFICANCE: These results may contribute to the design of thermal treatments of superficial melanoma through MMW-induced heating in the hyperthermic temperature range.

Age-dependence of electromagnetic power and heat deposition in near-surface tissues in emerging 5G bands.

With the development of 5th generation (5G) mobile networks people of different ages will be exposed in the upper part of the microwave spectrum. From the perspective of non-ionizing radiation dosimetry, an accurate analysis of age-dependent electromagnetic power deposition and resulting heating is required. In this study, we evaluate the effect of age on exposure at 26 GHz and 60 GHz. A near-surface tissue model illuminated by a plane wave is used to asses the exposure considering both frequency-independent and frequency-dependent limits. The age-related variation of the skin thickness and tissue electromagnetic properties has been considered. Moreover, the blood flow decrease rate has been taken into account to assess the age-dependent heating. Our results demonstrate that the overall variations of the power density, specific absorption rate (SAR) and heating in the near-surface tissues are limited to about 10-15%. These variations are mainly due to the tissue permittivity and blood flow change with age. In contrast to the transmitted power density that increases with age, the peak SAR decreases at both frequencies. The peak steady-state heating increases from 5 to 70 years old by roughly 11% at 26 GHz and 13% at 60 GHz.

Enhancement of Penetration of Millimeter Waves by Field Focusing Applied to Breast Cancer Detection.

OBJECTIVE: The potentialities of improving the penetration of millimeter waves for breast cancer imaging are here explored. METHODS: A field focusing technique based on a convex optimization method is proposed, capable of increasing the field level inside a breast-emulating stratification. RESULTS: The theoretical results are numerically validated via the design and simulation of two circularly polarized antennas. The experimental validation of the designed antennas, using tissue-mimicking phantoms, is provided, being in good agreement with the theoretical predictions. CONCLUSION: The possibility of focusing, within a lossy medium, the electromagnetic power at millimeter-wave frequencies is demonstrated. SIGNIFICANCE: Field focusing can be a key for using millimeter waves for breast cancer detection.

Absence of direct effect of low-power millimeter-wave radiation at 60.4 GHz on endoplasmic reticulum stress.

Millimeter waves (MMW) at frequencies around 60 GHz will be used in the very near future in the emerging local wireless communication systems and the potential health hazards of artificially induced environmental exposures represent a major public concern. The main aim of this study was to investigate the potential effects of low-power MMW radiations on cellular physiology. To this end, the human glial cell line, U-251 MG, was exposed to 60.4 GHz radiation at a power density of 0.14 mW/cm(2) and potential effect of MMW radiations on endoplasmic reticulum (ER) stress was investigated. ER is very sensitive to environmental insults and its homeostasis is altered in various pathologies. Through several assay systems, we found that exposure to 60.4 GHz does not modify ER protein folding and secretion, nor induces XBP1 or ATF6 transcription factors maturation. Moreover, expression of ER-stress sensor, BiP/GRP78 was examined by real-time PCR, in exposed or non-exposed cells to MMW radiations. Our data demonstrated the absence of significant changes in mRNA levels for BiP/GRP78. Our results showed that ER homeostasis does not undergo any modification at molecular level after exposure to low-power MMW radiation at 60.4 GHz. This report is the first study of ER-stress induction by MMW radiations.