Choosing the right electrode representation for modeling real bioelectronic interfaces: a comprehensive guide.

Objective.Producing realistic numerical models of neurostimulation electrodes in contact with the electrolyte and tissue, for use in time-domain finite element method simulations while maintaining a reasonable computational burden remains a challenge. We aim to provide a straightforward experimental-theoretical hybrid approach for common electrode materials (Ti, TiN, ITO, Au, Pt, IrOx) that are relevant to the research field of bioelectronics, along with all the information necessary to replicate our approach in arbitrary geometry for real-life experimental applications.Approach.We used electrochemical impedance spectroscopy (EIS) to extract the electrode parameters in the AC regime under different DC biases. The pulsed electrode response was obtained by fast amperometry (FA) to optimize and verify the previously obtained electrode parameters in a COMSOL Multiphysics model. For optimization of the electrode parameters a constant phase element (CPE) needed to be implemented in time-domain.Main results.We find that the parameters obtained by EIS can be used to accurately simulate pulsed response only close to the electrode open circuit potential, while at other potentials we give corrections to the obtained parameters, based on FA measurements. We also find that for many electrodes (Au, TiN, Pt, and IrOx), it is important to implement a distributed CPE rather than an ideal capacitor for estimating the electrode double-layer capacitance. We outline and provide examples for the novel time-domain implementation of the CPE for finite element method simulations in COMSOL Multiphysics.Significance.An overview of electrode parameters for some common electrode materials can be a valuable and useful tool in numerical bioelectronics models. A provided FEM implementation model can be readily adapted to arbitrary electrode geometries and used for various applications. Finally, the presented methodology for parametrization of electrode materials can be used for any materials of interest which were not covered by this work.

Implementation of a fully analog feedback loop with a Carbon-Black-based fractional order controller.

Fractional calculus is a mathematical framework that has attracted considerable interest from mathematicians, physicists, and engineers. Among its applications, the use of fractional calculus in the automatic control field has led to interesting results, such as more robust controllers, compared to their integer-order counterparts. The proposed work utilizes the physical realization of a solid-state fractional-order capacitor for the implementation of a fractional-order lead compensator. The proposed capacitor is realized using a carbon black-based dielectric. Therefore, a fully analog closed-loop system implementation is realized. A suitable case study is conducted to validate the controller performance, both from simulations and experimentally. The obtained results further confirm the possibility of realizing and applying a fully analog fractional-order controller.

Homogeneity Characterization of Textile-Integrated Wearable Sensors based on Impedance Spectroscopy.

One of the main challenges during the integration of a carbon/polymer-based nanocomposite sensor on textile substrates is the fabrication of a homogeneous surface of the nanocomposite-based thin films, which play a major role in the reproducibility of the sensor. Characterizations are therefore required in every fabrication step to control the quality of the material preparation, deposition, and curing. As a result, microcharacterization methods are more suitable for laboratory investigations, and electrical methods can be easily implemented for in situ characterization within the manufacturing process. In this paper, several textile-based pressure sensors are fabricated at an optimized concentration of 0.3 wt.% of multiwalledcarbon nanotubes (MWCNTs) composite material in PDMS. We propose to use impedance spectroscopy for the characterization of both of the resistive behavior and capacitive behavior of the sensor at several frequencies and under different loads from 50 g to 500 g. The impedance spectra are fitted to a model composed of a resistance in series with a parallel combination of resistance and a constant phase element (CPE). The results show that the printing parameters strongly influence the impedance behavior under different loads. The deviation of the model parameter α of the CPE from the value 1 is strongly dependent on the nonhomogeneity of the sensor. Based on an impedance spectrum measurement followed by parameter extraction, the parameter α can be determined to realize a novel method for homogeneity characterization and in-line quality control of textile-integrated wearable sensors during the manufacturing process.

Electrochemical Impedance Spectroscopy in the Characterisation and Application of Modified Electrodes for Electrochemical Sensors and Biosensors.

Electrochemical impedance spectroscopy is finding increasing use in electrochemical sensors and biosensors, both in their characterisation, including during successive phases of sensor construction, and in application as a quantitative determination technique. Much of the published work continues to make little use of all the information that can be furnished by full physical modelling and analysis of the impedance spectra, and thus does not throw more than a superficial light on the processes occurring. Analysis is often restricted to estimating values of charge transfer resistances without interpretation and ignoring other electrical equivalent circuit components. In this article, the important basics of electrochemical impedance for electrochemical sensors and biosensors are presented, focussing on the necessary electrical circuit elements. This is followed by examples of its use in characterisation and in electroanalytical applications, at the same time demonstrating how fuller use can be made of the information obtained from complete modelling and analysis of the data in the spectra, the values of the circuit components and their physical meaning. The future outlook for electrochemical impedance in the sensing field is discussed.

Effects of lead exposure on blood electrical impedance spectroscopy of mice.

BACKGROUND: Lead is a nonessential heavy metal, which can inhibit heme synthesis and has significant cytotoxic effects. Nevertheless, its effect on the electrical properties of red blood cells (RBCs) remains unclear. Consequently, this study aimed to investigate the electrical properties and the electrophysiological mechanism of lead exposure in mouse blood using Electrical Impedance Spectroscopy (EIS) in 0.01-100 MHz frequency range. Data characteristic of the impedance spectrum, Bodes plot, Nyquist plot and Nichols plot, and Constant Phase Element (CPE) equivalent circuit model were used to explicitly analyze the differences in amplitude-frequency, phase-frequency, and the frequency characteristics of blood in electrical impedance properties. RESULTS: Compared with the healthy blood in control mice, the changes in blood exposed to lead were as follows: (i) the hematocrit decreased; (ii) the amplitude-frequency and phase-frequency characteristics of electrical impedance decreased; (iii) the characteristic frequencies (f0) were significantly increased; (iv) the electrical impedance of plasma, erythrocyte membrane, and hemoglobin decreased, while the conductivity increased. (v) The pseudo-capacitance of cell membrane (CPE_Tm) and the intracellular pseudo-capacitance (CPE-Ti) were decreased. CONCLUSIONS: Therefore, EIS can be used as an effective method to monitor blood and RBC abnormalities caused by lead exposure. The electrical properties of the cells can be applied as an important observation in the evaluation of the toxic effects of heavy metals.

Impedance Response of a Thin Film on an Electrode: Deciphering the Influence of the Double Layer Capacitance.

The different contributions of the interfacial capacitance are identified in the case of passive materials or thin protective coatings deposited on the electrode surface. The method is based on a graphical analysis of the EIS results to determine both the passive-film capacitance in the high-frequency domain and the double-layer capacitance in the low-frequency domain. The proposed analysis is shown to be independent of the physicochemical origins of the frequency dispersion of the interfacial capacitances which results, from an analysis point of view of the experimental results, in the use of a constant-phase element However, for a correct evaluation of the thin-film properties such as its thickness, the high-frequency data must be corrected for the double-layer contribution. In particular, it is shown that if the double-layer capacitance gives a frequency-dispersed response, it is necessary to correct the high-frequency part for the double-layer constant-phase elements. This is first demonstrated on synthetic data and then used for the determination of the thickness of thin oxide film formed on Al in neutral pH solution.

Fractional-Order Chaotic Memory with Wideband Constant Phase Elements.

This paper provides readers with three partial results that are mutually connected. Firstly, the gallery of the so-called constant phase elements (CPE) dedicated for the wideband applications is presented. CPEs are calculated for 9° (decimal orders) and 10° phase steps including », ½, and ¾ orders, which are the most used mathematical orders between zero and one in practice. For each phase shift, all necessary numerical values to design fully passive RC ladder two-terminal circuits are provided. Individual CPEs are easily distinguishable because of a very high accuracy; maximal phase error is less than 1.5° in wide frequency range beginning with 3 Hz and ending with 1 MHz. Secondly, dynamics of ternary memory composed by a series connection of two resonant tunneling diodes is investigated and, consequently, a robust chaotic behavior is discovered and reported. Finally, CPEs are directly used for realization of fractional-order (FO) ternary memory as lumped chaotic oscillator. Existence of structurally stable strange attractors for different orders is proved, both by numerical analyzed and experimental measurement.

A Comparative Study of Two Fractional-Order Equivalent Electrical Circuits for Modeling the Electrical Impedance of Dental Tissues.

Background: Electrical impedance spectroscopy (EIS) is a fast, non-invasive, and safe approach for electrical impedance measurement of biomedical tissues. Applied to dental research, EIS has been used to detect tooth cracks and caries with higher accuracy than visual or radiographic methods. Recent studies have reported age-related differences in human dental tissue impedance and utilized fractional-order equivalent circuit model parameters to represent these measurements. Objective: We aimed to highlight that fractional-order equivalent circuit models with different topologies (but same number of components) can equally well model the electrical impedance of dental tissues. Additionally, this work presents an equivalent circuit network that can be realized using Electronic Industries Alliance (EIA) standard compliant RC component values to emulate the electrical impedance characteristics of dental tissues. Results: To validate the results, the goodness of fits of electrical impedance models were evaluated visually and statistically in terms of relative error, mean absolute error (MAE), root mean squared error (RMSE), coefficient of determination (R2), Nash-Sutcliffe's efficiency (NSE), Willmott's index of agreement (WIA), or Legates's coefficient of efficiency (LCE). The fit accuracy of proposed recurrent electrical impedance models for data representative of different age groups teeth dentin supports that both models can represent the same impedance data near perfectly. Significance: With the continued exploration of fractional-order equivalent circuit models to represent biological tissue data, it is important to investigate which models and model parameters are most closely associated with clinically relevant markers and physiological structures of the tissues/materials being measured and not just "fit" with experimental data. This exploration highlights that two different fractional-order models can fit experimental dental tissue data equally well, which should be considered during studies aimed at investigating different topologies to represent biological tissue impedance and their interpretation.

A detailed in-vitro study of Retinal pigment epithelium's growth as seen from the perspective of impedance spectroscopy analysis.

In this paper, we present a method to assess growth and maturation phases of the Retinal Pigment Epithelium (RPE) in-vitro at the cell layer level using impedance spectroscopy measurements on platinum electrodes. We extracted relevant parameters from an electrical circuit model fitted with the measured spectra. Based on microscopic imaging, the growth state of an independent culture developing in the same conditions is used as reference. We show that the confluence point is identified from a graphical analysis of the spectra transition as well as by observing a reconstructed parameter representing the average capacitance of the cell layer. More generally, this work presents a detailed investigation on how cell culture's state relates with either model parameter analysis or with graphical analysis of the measured spectra over a wide frequency band. While applied to the RPE, this work is also suitable for the study of any kind of monolayer epithelial cells growth.

Impedance spectroscopy study of the retinal pigment epithelium: Application to the monitoring of blue light exposure effect on A2E-loaded in-vitro cell cultures.

In age-related macular degeneration, the retinal pigment epithelium can be damaged by light acting on photosensitizers like N-retinylidene-N-retinylethanolamine (A2E). In this paper, the underlying cellular mechanism of lesion at the cell layer scale is analyzed by impedance spectroscopy. Retinal pigment epithelium (RPE) cells are cultured on top of custom-made electrodes capable of taking impedance measurements, with the help of a custom-made electronic setup but without the use of any chemical markers. An incubator is used to house the cells growing on the electrodes. An electrical model circuit is presented and linked to the constituents of the cell layer in which various electrical elements have been defined including a constant phase element (CPE) associated to the interface between the cell layer and the electrolyte. Their values are extracted from the fitted model of the measured impedance spectra. In this paper, we first investigate which parameters of the model can be analyzed independently. In that way, the parameter's evolution is examined with respect to two different targeted changes of the epithelium: 1. degradation of tight junctions between cells by extracellular calcium sequestration with Ethylenediaminetetraacetic acid (EDTA); 2. application of high amplitude short length electric field pulses. Based on the results obtained showing a clear relation between the model and the physiological state of the cell layer, the same procedure is applied to blue light exposure experiment. When A2E-loaded cells are exposed to blue light, the model parameters indicate, as expected, a clear degradation of the cell layer opposed to a relative stability of the not loaded ones.

Time Domain Characterization of the Cole-Cole Dielectric Model.

The Cole-Cole model for a dielectric is a generalization of the Debye relaxation model. The most familiar form is in the frequency domain and this manifests itself in a frequency dependent impedance. Dielectrics may also be characterized in the time domain by means of the current and charge responses to a voltage step, called response and relaxation functions respectively. For the Debye model they are both exponentials while in the Cole-Cole model they are expressed by a generalization of the exponential, the Mittag-Leffler function. Its asymptotes are just as interesting and correspond to the Curie-von Schweidler current response which is known from real-life capacitors and the Kohlrausch stretched exponential charge response.

Unique Constant Phase Element Behavior of the Electrolyte-Graphene Interface.

We report a unique constant phase element (CPE) behavior ( 1 Z = Q 0 ( j ω ) α ) of the electrolyte-graphene interface with both Q 0 and α showing dependence on the gate voltage. The frequency response of the electrolyte-graphene interface was studied using electrochemical impedance spectroscopy (EIS). The result suggests that (1) the electrolyte-graphene interface should be characterized as a CPE ( α < 1), rather than an ideal capacitor; and (2) both Q 0 and α show ambipolar dependence on the applied voltage. We speculate that the CPE behavior of the electrolyte-graphene interface arises from the charged impurities on the substrate and the defects in the graphene lattice, which could introduce inhomogeneity of local density of states (DOS). The low density of states of graphene makes α sensitive to these local DOS near the Dirac point, and thus showing dependence on the gate voltage. Measurement of the electrolyte-graphene interface capacitance based on multi-frequency capacitance-voltage (CV) profiling was demonstrated, and the extraction of the carrier mobility was performed. The study could lead to a more accurate understanding of the capacitive behavior of the electrolyte-graphene interface, which is instructive for the design and analysis of devices involving the electrolyte-graphene interface for nanoelectronics and bioelectronics applications.

Forced oscillation, integer and fractional-order modeling in asthma.

The purpose of this study was to evaluate the use of fractional-order (FrOr) modeling in asthma. To this end, three FrOr models were compared with traditional parameters and an integer-order model (InOr). We investigated which model would best fit the data, the correlation with traditional lung function tests and the contribution to the diagnostic of airway obstruction. The data consisted of forced oscillation (FO) measurements obtained from healthy (n=22) and asthmatic volunteers with mild (n=22), moderate (n=19) and severe (n=19) obstructions. The first part of this study showed that a FrOr was the model that best fit the data (relative distance: FrOr=4.3±2.4; InOr=5.1±2.6%). The correlation analysis resulted in reasonable (R=0.36) to very good (R=0.77) associations between FrOr parameters and spirometry. The closest associations were observed between parameters related to peripheral airway obstruction, showing a clear relationship between the FrOr models and lung mechanics. Receiver-operator analysis showed that FrOr parameters presented a high potential to contribute to the detection of the mild obstruction in a clinical setting. The accuracy [area under the Receiver Operating Characteristic curve (AUC)] observed in these parameters (AUC=0.954) was higher than that observed in traditional FO parameters (AUC=0.732) and that obtained from the InOr model (AUC=0.861). Patients with moderate and severe obstruction were identified with high accuracy (AUC=0.972 and 0.977, respectively). In conclusion, the results obtained are in close agreement with asthma pathology, and provide evidence that FO measurement associated with FrOr models is a non-invasive, simple and radiation-free method for the detection of biomechanical abnormalities in asthma.

Electrochemical impedance based chiral analysis of anti-ascorbutic drug: l-Ascorbic acid and d-ascorbic acid using C-dots decorated conductive polymer nano-composite electrode.

Clinical manifestations owing to l-ascorbic acid for scurvy as comparison to d-ascorbic acid and challenges of chiral purity are overcome by using chiral selective conductive polymer nanocomposite which mimics antibodies and enzymes. A novel chiral selective imprinted polyaniline-ferrocene-sulfonic acid film has been electrochemically fabricated on C-dots modified pencil graphite electrode. The performance of the obtained l-ascorbic acid or d-ascorbic acid chiral selective sensor was investigated by electrochemical impedance spectroscopy, cyclic and differential pulse voltammetry. The surface characteristics of the C-dots, chiral sensor before and after the de-doping of chiral d- and l-ascorbic acid were characterized by scanning electron microscopy, Raman spectroscopy and X-ray diffraction spectroscopy. Excellent recognition results were obtained by difference in electron transfer resistance. The proposed chiral sensor is capable of measuring d-ascorbic acid or l-ascorbic acid in aqueous as well as in real and commercial samples within the range of 0.020-0.187 nM and 0.003-0.232 nM with detection limit of 0.00073 nM and 0.00016 nM, respectively. The proposed method has also been examined for the chiral selective recognition of ascorbic acid isomers (d- and l-) quantitatively, in complicated matrices of real samples.

Rapid and molecular selective electrochemical sensing of phthalates in aqueous solution.

Reported research work presents real time non-invasive detection of phthalates in spiked aqueous samples by employing electrochemical impedance spectroscopy (EIS) technique incorporating a novel interdigital capacitive sensor with multiple sensing thin film gold micro-electrodes fabricated on native silicon dioxide layer grown on semiconducting single crystal silicon wafer. The sensing surface was functionalized by a self-assembled monolayer of 3-aminopropyltrietoxysilane (APTES) with embedded molecular imprinted polymer (MIP) to introduce selectivity for the di(2-ethylhexyl) phthalate (DEHP) molecule. Various concentrations (1-100 ppm) of DEHP in deionized MilliQ water were tested using the functionalized sensing surface to capture the analyte. Frequency response analyzer (FRA) algorithm was used to obtain impedance spectra so as to determine sample conductance and capacitance for evaluation of phthalate concentration in the sample solution. Spectrum analysis algorithm interpreted the experimentally obtained impedance spectra by applying complex nonlinear least square (CNLS) curve fitting in order to obtain electrochemical equivalent circuit and corresponding circuit parameters describing the kinetics of the electrochemical cell. Principal component analysis was applied to deduce the effects of surface immobilized molecular imprinted polymer layer on the evaluated circuit parameters and its electrical response. The results obtained by the testing system were validated using commercially available high performance liquid chromatography diode array detector system.

Frequency and Temperature Dependence of Fabrication Parameters in Polymer Dispersed Liquid Crystal Devices.

A series of polymer dispersed liquid crystal devices using glass substrates have been fabricated and investigated focusing on their electrical properties. The devices have been studied in terms of impedance as a function of frequency. An electric equivalent circuit has been proposed, including the influence of the temperature on the elements into it. In addition, a relevant effect of temperature on electrical measurements has been observed.

Biotic and abiotic characterization of bioanodes formed on oxidized carbon electrodes as a basis to predict their performance.

Bioelectrochemical systems (BESs) are based on the catalytic activity of biofilm on electrodes, or the so-called bioelectrodes, to produce electricity and other valuable products. In order to increase bioanode performance, diverse electrode materials and modification methods have been implemented; however, the factors directly affecting performance are yet unclear. In this work carbon cloth electrodes were modified by thermal, chemical, and electrochemical oxidation to enhance oxygenated surface groups, to modify the electrode texture, and consequently the electron transfer rate and biofilm adhesion. The oxidized electrodes were physically, chemically, and electrochemically characterized, then bioanodes were formed at +0.1 V vs. Ag/AgCl using domestic wastewater amended with acetate. The bioanode performance was evaluated according to the current and charge generated. The efficacy of the treatments were in the order Thermal>Electrochemical>Untreated>Chemical oxidation. The maximum current observed with untreated electrode was 0.152±0.026 mA (380±92 mA m(-2)), and it was increased by 78% and 28% with thermal and electrochemical oxidized electrodes, respectively. Moreover, the volatile solids correlated significantly with the maximum current obtained, and the electrode texture was revealed as a critical factor for increasing the bioanode performance.