Electromagnetic (EM) medical technologies are rapidly expanding worldwide for both diagnostics and therapeutics. As these technologies are low-cost and minimally invasive, they have been the focus of significant research efforts in recent years. Such technologies are often based on the assumption that there is a contrast in the dielectric properties of different tissue types or that the properties of particular tissues fall within a defined range. Thus, accurate knowledge of the dielectric properties of biological tissues is fundamental to EM medical technologies. Over the past decades, numerous studies were conducted to expand the dielectric repository of biological tissues. However, dielectric data is not yet available for every tissue type and at every temperature and frequency. For this reason, dielectric measurements may be performed by researchers who are not specialists in the acquisition of tissue dielectric properties. To this end, this paper reviews the tissue dielectric measurement process performed with an open-ended coaxial probe. Given the high number of factors, including equipment- and tissue-related confounders, that can increase the measurement uncertainty or introduce errors into the tissue dielectric data, this work discusses each step of the coaxial probe measurement procedure, highlighting common practices, challenges, and techniques for controlling and compensating for confounders.

https://www.mdpi.com/2075-4418/8/2/40/pdf

Open-ended coaxial probe technique for dielectric measurement of biological tissues: challenges and common practices

Electroporation is being successfully used in biology, medicine, food processing, and biotechnology, and in some environmental applications. Recent applications also include in addition to classical electroporation, where cells are exposed to micro- or milliseconds long pulses, exposures to extremely short nanosecond pulses, i.e., high-frequency electroporation. Electric pulses are applied to cells in different structural configurations ranging from suspended cells to cells in tissues. Understanding electroporation of cells in tissues and other complex environments is a key to its successful use and optimization in various applications. Thus, explanation will be provided theoretically/numerically with relation to experimental observations by scaling our understanding of electroporation from the molecular level of the cell membrane up to the tissue level.

Tutorial: Electroporation of cells in complex materials and tissue

Human skin consists of several layers with distinct dielectric properties. Physiological processes leading to changes in dielectric properties of the specific layers can potentially be non-invasively monitored employing dielectric spectroscopy. So far no comprehensive skin and underlying tissue model is available for this purpose in the frequency range between 1 and 100 MHz. Focusing on this dispersion-dominated frequency region, different multilayer skin models are investigated. First, with sublayers obtained from two-phase mixtures, second, three-phase mixtures of shelled cell-like ellipsoids and finally, multiphase mixtures obtained from numerical models of single cells generated using a flexible surface parametrization method. All models are numerically evaluated using the finite-element method and a fringing field sensor on the top of the multilayer system serving as a probe. Furthermore, measurements with the sensor probing skin in vivo were performed. The validity of the models was tested by removing the uppermost skin layer, the stratum corneum (SC). It was found that only a three-phase mixture (extracellular medium, cell membrane and cytoplasm) at least can qualitatively reproduce the measured dispersion still occurring without the SC if the model is set up without a priori knowledge of the dispersive behaviour as e.g. a Cole–Cole fit to measured data. Consequently, microstructural features of tissue have to be part of any accurate skin model in the MHz region.

https://iopscience.iop.org/article/10.1088/0022-3727/45/2/025301/pdf

Modelling and validation of dielectric properties of human skin in the MHz region focusing on skin layer morphology and material composition

Simulations probing the conductivity changes of three-dimensional models of biological tissues consisting of random ternary core-shell sphere packings with different spatial scales are described. We investigate the temporal evolution of the electric conductivity of these packings during application of an electric field with magnitude either below or above the value leading to cell membrane electroporation. The fraction of electroporated cells can be described by a hyperbolic tangent function of the electric field. The collective physical processes causing the transient permeability of the cell membranes can be understood by analogy with the physics of a two-state system with an external field.

/pdf/a-numerical-analysis-of-multicellular-environment-for-2mpfh5e8s5.pdf

A numerical analysis of multicellular environment for modeling tissue electroporation

In this paper we study the read range of implanted sensors based on batteryless, Near-Field Communication (NFC) integrated circuits (IC) using an NFC-equipped smartphone as a reader. The most important challenges are the low coupling between loops of different sizes, the limited quality factor imposed by the bandwidth communication, the effects of the body on propagation, and the detuning of the antennas. Two systems are analyzed: a conventional system based on resonant coupling between two coils; and a system based on resonant coupling between three coils. With the latter, a relay antenna is attached to a patch, which is adhered to the skin. Simulations and measurements show that the quality factor of both antennas can be improved by including a spacer made of low-permittivity material. A circuit model is proposed for the implanted and relay antenna, which simplifies its usage in circuit simulators. Some implanted and relay antenna prototypes are analyzed and a system model that includes a nonlinear model of the tag is used to analyze the maximum depth at which the implant can be read. Our experimental results show that the system based on three coils performs much better performance at longer distances and is more robust to misalignments between coils. A 15×15 mm-implanted tag with commercial NFC IC and energy harvesting can be read using commercial smartphones. It can feed sensors at a distance of up to 16 mm inside the body and at a distance of 3 cm from the skin. Our results also show that data previously stored in the IC memory can be transferred to the reader located at distances of up to 2 cm and 3.8 cm for the 2-coil and 3-coil systems, respectively. This study demonstrates the potential of batteryless NFC sensors for biomedical and wearable applications using mobile phones as readers.

/pdf/study-on-the-reading-of-energy-harvested-implanted-nfc-tags-42s6ttnhqu.pdf

Study on the Reading of Energy-Harvested Implanted NFC Tags Using Mobile Phones

The human skin consists of several layers with distinct dielectric properties. Resolving the impact of changes in dielectric parameters of skin layers and predicting them allows for non-invasive sensing in medical diagnosis. So far no complete skin and underlying tissue model is available for this purpose in the MHz range. Focusing on this dispersiondominated frequency region multilayer skin models are investigated: First, containing homogeneous non-dispersive sublayers and second, with sublayers obtained from a three-phase Maxwell-Garnett mixture of shelled cell-like ellipsoids. Both models are numerically simulated using the Finite Element Method, a fringing field sensor on the top of the multilayer system serving as a probe. Furthermore, measurements with the sensor probing skin in vivo are performed. In order to validate the models the uppermost skin layer, the stratum corneum was i) included and ii) removed in models and measurements. It is found that only the Maxwell-Garnett mixture model can qualitatively reproduce the measured dispersion which still occurs without the stratum corneum and consequently, structural features of tissue have to be part of the model.

Validation of human skin models in the MHz region

In the past, mainly analytical mixing formulas were used for modeling of dielectric properties of biological cells. General drawbacks of such formulas are the restriction to simple shapes and small cellular volume fractions. Assuming cell suspensions or tissues being quasi-periodic the problem size can be reduced to a cubic unit cell containing a single biological cell. Under this assumption numerical, e.g. Finite- Element models of such unit cells provide effective dielectric parameters for the entire tissue or cell suspension. In this work a flexible shape parametrization method allowing for a realistic representation of biological cells is applied to eight different cell types. A non-axisymmetric columnar epithelium cell occurring e.g. in the epidermis is chosen as an example. Numerical simulations of the columnar cell exposed to a time-harmonic electric field are performed for two different, high volume fractions, followed by the extraction of effective dielectric parameters of the bulk material. The simulation results are compared to two analytical approximations for ellipsoidal particles. The results suggest, that the calculation of effective dielectric properties of arbitrarily shaped cells in the frequency range between 100kHz and 1GHz requires at least a numerical cell model.

Towards a realistic dielectric tissue model: A multiscale approach

Accurate Multiscale Skin Model Suitable for Determining the Sensitivity and Specificity of Changes of Skin Components

An efficient and versatile numerical method for the generation of different realistically shaped biological cells is developed. This framework is used to calculate the dielectric spectra of materials containing specific types of biological cells. For the generation of the numerical models of the cells a flexible parametrization method based on the so-called superformula is applied including the option of obtaining non-axisymmetric shapes such as box-shaped cells and even shapes corresponding to echinocytes. The dielectric spectra of effective media containing various cell morphologies are calculated focusing on the dependence of the spectral features on the cell shape. The numerical method is validated by comparing a model of spherical inclusions at a low volume fraction with the analytical solution obtained by the Maxwell‐Garnett mixing formula, resulting in good agreement. Our simulation data for different cell shapes suggest that around 1MHz the effective dielectric properties of different cell shapes at different volume fractions significantly deviate from the spherical case. The most pronounced change exhibits ! eff between 0.1 and 1MHz with a deviation of up to 35% for a box-shaped cell and 15% for an echinocyte compared with the sphere at a volume fraction of 0.4. This hampers the unique interpretation of changes in cellular features measured by dielectric spectroscopy when simplified material models are used. (Some figures in this article are in colour only in the electronic version)

https://iopscience.iop.org/article/10.1088/0022-3727/43/36/365405/pdf

Modelling effective dielectric properties of materials containing diverse types of biological cells

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