Electrical Bioimpedance Analysis for Evaluating the Effect of Pelotherapy on the Human Skin: Methodology and Experiments.

BACKGROUND: Pelotherapy is the traditional procedure of applying curative muds on the skin's surface-shown to have a positive effect on the human body and cure illnesses. The effect of pelotherapy is complex, functioning through several mechanisms, and depends on the skin's functional condition. The current research objective was to develop a methodology and electrodes to assess the passage of the chemical and biologically active compounds of curative mud through human skin by performing electrical bioimpedance (EBI) analysis. METHODS: The methodology included local area mud pack and simultaneous tap water compress application on the forearms with the comparison to the measurements of the dry skin. A custom-designed small-area gold-plated electrode on a rigid printed circuit board, in a tetrapolar configuration, was designed. A pilot study experiment with ten volunteers was performed. RESULTS: Our results indicated the presence of an effect of pelotherapy, manifested by the varying electrical properties of the skin. Distinguishable difference in the measured real part of impedance (R) emerged, showing a very strong correlation between the dry and tap-water-treated skin (r = 0.941), while a poor correlation between the dry and mud-pack-treated skin (r = 0.166) appeared. The findings emerged exclusively in the frequency interval of 10 kHz …1 MHz and only for R. CONCLUSIONS: EBI provides a promising tool for monitoring the variations in the electrical properties of the skin, including the skin barrier. We foresee developing smart devices for promoting the exploitation of spa therapies.

Derivation of Bioimpedance Model Data Utilizing a Compact Analyzer and Two Capacitive Electrodes: A Forearm Example.

The paper investigates the impacts of the selected electrical equivalent circuit model, measurement setup, and surrounding environment on the trustworthiness of electrical bioimpedance measurement and obtained model data in the human body. The influence of these constitutive components of the system on finding the model parameters is analyzed and illustrated with examples. The results based on experimental measurements on a forearm near the wrist are provided by employing the model, measurement setup, and novel 16-bit compact wireless impedance analyzer (CIA) according to the outcome of the analysis. The area near the wrist is of interest because of attempts to get cardiac-activity-related impedance changes. It is concluded that a two-electrode system with voltage excitation suits better for determining bioimpedance model parameters in the ß dispersion area. The results obtained with the CIA and two capacitive bracelet electrodes on a left forearm were used for the fitting model parameters. Despite the small dimensions of 60 × 60 × 25 mm of the CIA reducing stray capacitance to 8 pF, it provides relative impedance magnitude measurement error below 0.3% and phase error below 0.2 ° in the 10 MHz range. Analysis of the model parameters allowed separation of the electrodes, skin, and internal tissue spectra and revealed the relative significance of model components at different frequencies.

Budded baculoviruses as a receptor display system to quantify ligand binding with TIRF microscopy.

Studying mechanisms of receptor-ligand interactions has remained challenging due to several limitations of different measurement methods. Here we present a total internal reflection fluorescence microscopy-based method that maintains the right balance between retaining the receptors in the natural lipid environment, sufficient throughput for ligand screening, high sensitivity, and offering more detailed view into the ligand-binding process. The novel method combines G protein-coupled receptor display in budded baculovirus particles and the immobilization of the particles to a functionalized coverslip. We adapted and validated the functionalized coverslip preparation process to achieve selective immobilization of budded baculovirus particles. The selectivity of budded baculovirus immobilization was validated with budded baculovirus particles displaying either Frizzled 6 receptors labeled with mCherry or neuropeptide Y Y1 receptors. To scale the system for ligand binding assays, we developed both open-source multiwell systems and image analysis software SPOTNIC for flexible assay design. The neuropeptide Y Y1 receptor was used for further receptor-ligand binding studies with high-affinity TAMRA labeled fluorescent ligand UR-MC026. The affinities of the fluorescent ligand and four unlabeled ligands (BIBO3304, UR-MK299, PYY, pNPY) were obtained with the developed method and followed a similar trend with both the parallel measurements with fluorescence anisotropy method and the data published earlier. The novel method could be extended for various advanced assays utilizing multidimensional detection modes, integrating super-resolution methods for single molecule detection and microfluidic devices for kinetic measurements.

Methods for Detection of Bioimpedance Variations in Resource Constrained Environments.

Changes in a certain parameter are often a few magnitudes smaller than the base value of the parameter, specifying significant requirements for the dynamic range and noise levels of the measurement system. In case of electrical bioimpedance acquisition, the variations can be 1000 times smaller than the entire measured value. Synchronous or lock-in measurement of these variations is discussed in the current paper, and novel measurement solutions are presented. Proposed methods are simple and robust when compared to other applicable solutions. A common feature shared by all members of the group of the proposed solutions is differentiation. It is achieved by calculating the differences between synchronously acquired consecutive samples, with lock-in integration and analog differentiation. All these methods enable inherent separation of variations from the static component of the signal. The variable component of the bioimpedance can, thus, be acquired using the full available dynamic range of the apparatus for its detection. Additive disturbing signals and omnipresent wideband noise are considered and the method for their reduction is proposed.

Multichannel Electrical Impedance Spectroscopy Analyzer with Microfluidic Sensors.

Impedance spectroscopy is a common approach in assessing passive electrical properties of biological matter. However, several problems appear in microfluidic devices in connection with the requirement for high sensitivity of signal acquisition from small volume sensors. The developed compact and inexpensive analyzer provides impedance spectroscopy measurement from three sensors, both connected in direct and differential modes. Measurement deficiencies are reduced with a novel design of sensors, measurement method, optimized electronics, signal processing, and mechanical design of the analyzer. Proposed solutions are targeted to the creation of reliable point-of-care (POC) diagnostic and monitoring appliances, including lab-on-a-chip type devices in the next steps of development. The test results show the good working ability of the developed analyzer; however, also limitations and problems that require attention and further improvement are appointed.

Our Journal is Entering into its Second Decade.

The first issue of the Journal of Electrical Bioimpedance saw the light in 2010 by the personal initiative of two men from the University of Oslo, Prof. Sverre Grimnes and Prof. Ørjan G. Martinsen, who has been the editor-in-chief of our Journal during all these ten years. With the sense of gratitude, we hope that he continues his persistent work also during the approaching next decade in the new conditions with a growing number of bioimpedance publications worldwide. However, every success creates new problems, some of which are discussed below.

On the Selection of Excitation Signals for the Fast Spectroscopy of Electrical Bioimpedance.

Different excitation signals are applicable in the wideband impedance spectroscopy in general. However, in electrical bioimpedance (EBI) measurements, there are limitations that set specific demands on the properties of the excitation signals. This paper compares the efficiency of different excitation signals in a graspable presentation and gives recommendations for their use. More exactly, the paper deals with finding the efficient excitation waveforms for the fast spectroscopy of electrical bioimpedance. Nevertheless, the described solutions could be useful also in other implementations of impedance spectroscopy intended for frequency domain characterization of different objects.

Broadband discrete-level excitations for improved extraction of information in bioimpedance measurements.

The implementation of bioimpedance-based methods in implantable and wearable medical devices requires simple, cheap and low energy consuming measurement settings for enabling impedance spectroscopy at a wide range of frequencies. In the present paper, such a wideband bioimpedance measurement method is discussed, which embodies two-channel impedance measurement for monitoring of the frequency-dependent phase shift between the channels (phase spectrum). In addition, the improved resolution is achieved by employing comparative measurements by introducing the predetermined reference impedance into one of the measurement channels. The proposed and analyzed measurement system uses a binary excitation signal that simplifies signal generation and processing hardware and does not need sophisticated software--low-complexity devices can be designed this way. It is shown that in particular the binary chirp excitation has some essential advantages compared with its counterparts--the maximum length sequence and binary multifrequency excitations. The spectra of chirps of the binary chirp excitation, including their discrete-level modifications, are continuous and flat at the same time. Due to the independent scalability in time and frequency domains and very high chirping rate, the chirps are especially suitable as excitation signals for wideband spectroscopy of dynamic objects with changing impedances in devices such as implantable heart monitors, pacemakers and high-throughput microfluidic lab-on-chip-type devices for performing bioimpedance-based monitoring of cells and droplets.

Crest factor optimization of the multisine waveform for bioimpedance spectroscopy.

The multisine excitation is widely used in impedance measurements to retain the advantages of the sine wave, while reducing the measurement time. Adding up sine waves increases the amplitude of the excitation signal, but, for the linearity assumption to be valid, the overall amplitude of the signal needs to be kept low. Thus, the crest factor (CF) of the excitation signal must be minimized. A novel empirical method for the minimization of the CF is described in this paper. As in the case of other known methods, the computed CF may be guaranteed to be only a local minimum. However, a systematic variation of initial parameters, which is possible due to the sparing algorithm, ensures a CF value very close or equal to the global minimum. The results of CF minimization and comparison with the results from other sources are provided. The direct CF optimization results (set of optimal phases) are not well suited for practical implementation. The influence of phase accuracy on the CF is discussed, and an algorithm for the recalculation of initial phases to the rougher set is described. It is shown that previously obtained optimization results (minimal CF) can be highly preserved, even in the case of rough phase resolutions. The CF of the multisine also depends on the frequency distribution and amplitudes of its components. The CF of multisines with several frequency distributions are compared.

Wearable system for non-invasive and continuous monitoring central aortic pressure curve and augmentation index.

The paper presents a non-invasive method and system for a long-term and continuous monitoring of the central aortic pressure (CAP) waveform and the augmentation index (AI). The CAP curve is estimated from the measured radial electrical bio-impedance (EBI) using spectral domain transfer functions (TF), which are established on the basis of data analysis during clinical experiments. Experiments were carried out on 3 volunteers by now. During the experiment, a 0.5 mg sublingual nitroglycerin tablet was administrated to each volunteer. Both, the reconstructed CAP curve and the AI have very good correlation with the results obtained by the SphygmoCor system. But, in opposite to the traditional tonometry based CAP curve and AI estimation methods, the proposed one is more convenient to use and allows continuous and long-term personalized monitoring of the CAP curve and of the AI.

Wearable data acquisition system of multimodal physiological signals for personal health care.

The paper proposes a wearable multimodal data acquisition system for biological signals. The system enables logging of electrical bioimpedance signals from multiple electrodes, electrocardiographic signals (ECG), acceleration signals from multiple locations, and spirometric data from a moving object. Later it will be used to conduct field measurements for characterizing health of the object under investigation. Main goal is to acquire enough data for development, refinement, and simplification of signal processing algorithms. The system is center part of the new wearable compact data acquisition modules ZCardio. Those modules enable multichannel impedance spectroscopy by logging ECG signals and data from the spirometric sensor. Initial reference measurements were conducted. Alternatively, tests were performed using Plessey Semiconductors capacitive sensors. Acceleration signals are gathered.

Binary signals in impedance spectroscopy.

Using of binary waveforms in the fast impedance spectroscopy of biological objects is discussed in the paper. There is shown that the energy of binary waveforms can be concentrated onto selected separate frequencies. We can optimize the binary excitation waveform depending on the shape of frequency response of the impedance under study to maximize the levels of signal components with certain selected frequencies. As a result, we are able to receive maximal amount of information about the properties and behavior of the impedance to be studied. We have designed and prototyped the impedance spectroscopy device operating in the frequency range from 100 mHz to 500 kHz to cover α- and ß-regions of the bio-impedance spectrum of time-varying subjects as, for example, fast moving cells in micro-fluidic devices, beating heart and breathing lungs or the whole cardiovascular system.

Online tissue discrimination for transcutaneous needle guidance applications using broadband impedance spectroscopy.

This paper reports on a novel system architecture for measuring impedance spectra of a biological tissue close to the tip of a hollow needle. The measurement is performed online using fast broadband chirp signals. The time domain measurement raw data are transformed into the transfer function of the tissue in frequency domain. Correlation technique is used to analyze the characteristic shape of the derived tissue transfer function with respect to known "library functions" for different types of tissue derived in earlier experiments. Based on the resulting correlation coefficients the exact type of tissue is determined. A bipolar coaxial needle is constructed, simulated by finite element method and tested during various in vitro and in vivo experiments. The results show a good spatial resolution of approximately 1.0 mm for a needle with a diameter of 2.0 mm. The correlation coefficients for the three tested tissue types muscle, fat, and blood allow for a clear tissue classification. Best results have been obtained using the characteristic phase diagrams for each tissue. Correlated to the corresponding library transfer function the coefficients are in the range of +0.96 to +0.99 for the matching tissue. In return, the resulting coefficients for correlation with nonmatching tissues are in the range of -0.93 to +0.81.

Improvements in design of spectra of multisine and binary excitation signals for multi-frequency bioimpedance measurement.

The paper discusses the usability of multi-frequency binary waveforms for broadband excitation in fast measurements of impedance spectrum of biological objects. It is shown that up to 70% of the energy of the amplitude spectrum of such two-level binary signals can be concentrated into the selected separate frequencies. The levels of selected frequency components are controllable in tens and hundreds of times. In this way we can underline the most important frequencies enhancing the corresponding amplitudes in the spectrum of excitation signal. As an implementation example, we consider the impedance spectroscopy in micro-fluidic devices for inline measurement of the conductivity of droplets in segmented flow. We use a thin-walled glass capillary with electrodes contacting the outer surface so that the contactless measurement of conductivity of liquid with biologic cells becomes possible.

Intracardiac electrical bioimpedance as a basis for controlling of pacing rate limits.

Intracardiac impedance can provide real-time hemodynamic information to automatically control the lower and upper rate limits of a rate-adaptive pacemaker. It is necessary to overcome a number of technical challenges to accomplish this within the constraints of an implantable device.