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.

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.

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.

Millimeter-wave pulsed heating in vitro: cell mortality and heat shock response.

Millimeter wave (MMW)-induced heating represents a promising alternative for non-invasive hyperthermia of superficial skin cancer, such as melanoma. Pulsed MMW-induced heating of tumors allows for reaching high peak temperatures without overheating surrounding tissues. Herein, for the first time, we evaluate apoptotic and heat shock responses of melanoma cells exposed in vitro to continuous (CW) or pulsed-wave (PW) amplitude-modulated MMW at 58.4 GHz with the same average temperature rise. Using an ad hoc exposure system, we generated 90 min pulse train with 1.5 s pulse duration, period of 20 s, amplitude of 10 °C, and steady-state temperature at the level of cells of 49.2 °C. The activation of Caspase-3 and phosphorylation of HSP27 were investigated using fluorescence microscopy to monitor the spatial variation of cellular response. Our results demonstrate that, under the considered exposure conditions, Caspase-3 activation was almost 5 times greater following PW exposure compared to CW. The relationship between the PW-induced cellular response and SAR-dependent temperature rise was non-linear. Phosphorylation of HSP27 was 58% stronger for PW compared to CW. It exhibits a plateau for the peak temperature ranging from 47.7 to 49.2 °C. Our results provide an insight into understanding of the cellular response to MMW-induced pulsed heating.

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 unveil alterations of biomembranes permeability in human HaCaT keratinocytes upon 60 GHz millimeter-wave exposure.

A joint metabolomic and lipidomic workflow is used to account for a potential effect of millimeter waves (MMW) around 60 GHz on biological tissues. For this purpose, HaCaT human keratinocytes were exposed at 60.4 GHz with an incident power density of 20 mW/cm², this value corresponding to the upper local exposure limit for general public in the context of a wide scale deployment of MMW technologies and devices. After a 24h-exposure, endo- and extracellular extracts were recovered to be submitted to an integrative UPLC-Q-Exactive metabolomic and lipidomic workflow. R-XCMS data processing and subsequent statistical treatment led to emphasize a limited number of altered features in lipidomic sequences and in intracellular metabolomic analyses, whatever the ionization mode (i.e 0 to 6 dysregulated features). Conversely, important dysregulations could be reported in extracellular metabolomic profiles with 111 and 99 frames being altered upon MMW exposure in positive and negative polarities, respectively. This unexpected extent of modifications can hardly stem from the mild changes that could be reported throughout transcriptomics studies, leading us to hypothesize that MMW might alter the permeability of cell membranes, as reported elsewhere.

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.

Tissue-mimicking materials for breast phantoms up to 50 GHz.

Millimeter (mm)-wave imaging has been recently proposed as a new technique for breast cancer detection, based on the significant dielectric contrast between healthy and tumor tissues. Here we propose a procedure to fabricate, electromagnetically characterize and preserve realistic breast tissue-mimicking phantoms for testing mm-wave imaging prototypes. Low-cost, non-toxic and easy-to-produce mixtures made of sunflower oil, water and gelatin were prepared and their dielectric properties were for the first time measured in the (0.5-50) GHz frequency range using a coaxial probe kit. Different oil and gelatin percentages were tested. An alternative recipe based on a waste-oil hardener was also proposed. Finally, water and sunflower oil were investigated as preservation media. The mixtures electromagnetic properties were in good agreement with those of human breast ex vivo samples. By changing the ingredient concentrations or using different solidifying agents it was possible to mimic different tissue types. Besides, we show that sunflower oil represents an effective preservation medium for the developed materials. The first breast phantom mimicking a tumor mass into healthy tissues up to 50 GHz was also successfully fabricated. Results demonstrated the potential of the designed recipes to mimic breast tissues with different biological characteristics, preserving dielectric properties over time. Thus, this study represents a fundamental step towards the development of heterogeneous breast phantoms able to mimic the electromagnetic behavior of healthy and tumor tissues for mm-wave imaging applications.

Immune-to-Detuning Wireless In-Body Platform for Versatile Biotelemetry Applications.

BACKGROUND AND OBJECTIVE: In-body biotelemetry devices enable wireless monitoring of a wide range of physiological parameters. These devices rely on antennas to interface with external receivers, yet existing systems suffer from impedance detuning caused by the substantial differences in electromagnetic properties among various tissues. In this paper, we propose an immune-to-detuning in-body biotelemetry platform featuring a novel tissue-independent antenna design. METHODS: Our approach uses a novel slot-patch conformal antenna integrated into a flexible polyimide printed circuit board containing the device circuitry and encapsulated within a 17.7 mm [Formula: see text]8.9 mm biocompatible shell. The antenna is synthesized and optimized using a hybrid analytical-numerical approach and, then, characterized numerically and experimentally in terms of impedance stability. RESULTS: The proposed platform shows stable impedance, whereas operating in any mammalian tissue as well as in air. The system is optimized for the 434-MHz industrial, scientific, and medical band and can easily be returned for any MedRadio band in the 401-457-MHz spectrum. CONCLUSION: Ultrarobust impedance characteristics were achieved. Without any modifications, the proposed biotelemetry platform can be used, for instance, as an ingestible for humans or as an implantable for a wide range of animals: from rodents to cattle.

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.

Effect of acute millimeter wave exposure on dopamine metabolism of NGF-treated PC12 cells.

Several forthcoming wireless telecommunication systems will use electromagnetic frequencies at millimeter waves (MMWs), and technologies developed around the 60-GHz band will soon know a widespread distribution. Free nerve endings within the skin have been suggested to be the targets of MMW therapy which has been used in the former Soviet Union. So far, no studies have assessed the impact of MMW exposure on neuronal metabolism. Here, we investigated the effects of a 24-h MMW exposure at 60.4 GHz, with an incident power density (IPD) of 5 mW/cm², on the dopaminergic turnover of NGF-treated PC12 cells. After MMW exposure, both intracellular and extracellular contents of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were studied using high performance liquid chromatography. Impact of exposure on the dopamine transporter (DAT) expression was also assessed by immunocytochemistry. We analyzed the dopamine turnover by assessing the ratio of DOPAC to DA, and measuring DOPAC accumulation in the medium. Neither dopamine turnover nor DAT protein expression level were impacted by MMW exposure. However, extracellular accumulation of DOPAC was found to be slightly increased, but not significantly. This result was related to the thermal effect, and overall, no evidence of non-thermal effects of MMW exposure were observed on dopamine metabolism.

Personal Exposimeter for Radiation Assessment in Real Environments in the 60-GHz Band.

For the first time, a personal exposimeter (PEX) for 60 GHz radiation measurements is presented. The PEX is designed based on numerical simulations and both on-body and on-phantom calibration measurements to determine the antenna aperture and measurement uncertainty of the PEX. The measurement uncertainty of the PEX is quantified in terms of 50 and 95% prediction intervals of its response. A PEX consisting of three nodes (antennas) with VHH (vertical-horizontal-horizontal) polarization results in a 95% prediction interval of 6.6 dB. A 50% prediction interval of 1.3 dB (factor of 1.3) is obtained for measured power densities which is 3.1 dB lower than a single antenna experiment. The uncertainty is 19.7 dB smaller than that of existing commercial exposimeters at lower frequencies (≤6GHz).

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.