Electrodermal responses to discrete stimuli measured by skin conductance, skin potential, and skin susceptance.

BACKGROUND/AIM: Presently, electrodermal activity (EDA) is the preferred term for changes in electrical properties of the skin. Change in the skin conductance responses (SCRs) and skin potential responses (SPRs) due to external stimuli have previously been investigated in a number of studies, but very little for skin susceptance responses (SSRs) recorded simultaneously at the same skin site. This study aimed to investigate the association between the three parameters of EDA, skin conductance (SC), skin potential (SP), and skin susceptance (SS) responses generated by different types of psychological stimuli. METHODS: SCRs, SPRs, and SSRs were recorded from 20 healthy test subjects simultaneously at the same skin area. EDA responses were induced by five different external stimuli, which were shown in the form of PowerPoint slides on a PC monitor that situated in front of participants. RESULTS: All stimuli evoked EDA responses, but with significantly different magnitudes, dependent on stimulus type. Both SC and SP waveforms yielded positive responses with respect to the stimuli; however, SS showed negative response and its role was found to be significant at low frequency (20 Hz). CONCLUSIONS: This study illustrated that different discrete stimuli showed different passive and active electrodermal responses at the same skin site. SCRs, SPRs, and SSRs were dependent on the stimulus type, and the highest response was associated with the sound stimulus, which can be attributed to orienting response or startle reflex. In addition, it was found that the SSRs have a significant contribution at 20 Hz. In spite of a high correlation found between average amplitude values of SCRs and SSRs, no significant association was seen between average amplitudes values of SPRs and SSRs, and between SCRs and SPRs.

An impedance method for spatial sensing of 3D cell constructs--towards applications in tissue engineering.

We present the characterisation and validation of multiplexed 4-terminal (4T) impedance measurements as a method for sensing the spatial location of cell aggregates within large three-dimensional (3D) gelatin scaffolds. The measurements were performed using an array of four rectangular chambers, each having eight platinum needle electrodes for parallel analysis. The electrode positions for current injection and voltage measurements were optimised by means of finite element simulations to maximise the sensitivity field distribution and spatial resolution. Eight different 4T combinations were experimentally tested in terms of the spatial sensitivity. The simulated sensitivity fields were validated using objects (phantoms) with different conductivity and size placed in different positions inside the chamber. This provided the detection limit (volume sensitivity) of 16.5%, i.e. the smallest detectable volume with respect to the size of the measurement chamber. Furthermore, the possibility for quick single frequency analysis was demonstrated by finding a common frequency of 250 kHz for all the presented electrode combinations. As final proof of concept, a high density of human hepatoblastoma (HepG2) cells were encapsulated in gelatin to form artificial 3D cell constructs and detected when placed in different positions inside large gelatin scaffolds. Taken together, these results open new perspectives for impedance-based sensing technologies for non-invasive monitoring in tissue engineering applications providing spatial information of constructs within biologically relevant 3D environments.

Sorption properties of the human stratum corneum.

Water sorption is important for the overall structure and function of keratinized tissues such as the human epidermal stratum corneum (SC). In this study we report on a gravimetric method for studying sorption properties of human SC, both from heel and female breast skin. Changes in mass were measured as the relative humidity was altered in steps under controlled environmental conditions. The possibility of hysteresis is also discussed. Furthermore, we have found that the sorption time constants show triphasic behaviour during absorption, but not during desorption. This behaviour is connected to the 3 different types of water present in the SC. Water also enters the SC much more rapidly compared to its exit at relative humidities <50%. Finally, the amount of time between sample preparation and onset of measurement seems to have an effect on the absorption rate, but less on the total amount of water absorbed.

Finite Element Simulation of the Impedance Response of a Vascular Segment as a Function of Changes in Electrode Configuration.

Monitoring a biological tissue as a three dimensional (3D) model is of high importance. Both the measurement technique and the measuring electrode play substantial roles in providing accurate 3D measurements. Bioimpedance spectroscopy has proven to be a noninvasive method providing the possibility of monitoring a 3D construct in a real time manner. On the other hand, advances in electrode fabrication has made it possible to use flexible electrodes with different configurations, which makes 3D measurements possible. However, designing an experimental measurement set-up for monitoring a 3D construct can be costly and time consuming and would require many tissue models. Finite element modeling methods provide a simple alternative for studying the performance of the electrode and the measurement set-up before starting with the experimental measurements. Therefore, in this study we employed the COMSOL Multiphysics finite element modeling method for simulating the effects of changing the electrode configuration on the impedance spectroscopy measurements of a venous segment. For this purpose, the simulations were performed for models with different electrode configurations. The simulation results provided us with the possibility of finding the optimal electrode configuration including the geometry, number and dimensions of the electrodes, which can be later employed in the experimental measurement set-up.

Monitoring the quality of frozen-thawed venous segments using bioimpedance spectroscopy.

OBJECTIVE: Storage at temperatures as low as -80 °C and below (cryopreservation) is considered a method for long-term preservation of cells and tissues, and especially blood vessel segments, which are to be used for clinical operations such as transplantation. However, the freezing and thawing processes themselves can induce injuries to the cells and tissue by damaging the structure and consequently functionality of the cryopreserved tissue. In addition, the level of damage is dependent on the rate of cooling and warming used during the freezing-thawing process. Current methods for monitoring the viability and integrity of cells and tissues after going through the freezing-thawing cycle are usually invasive and destructive to the cells and tissues. Therefore, employing monitoring methods which are not destructive to the cryopreserved tissues, such as bioimpedance measurement techniques, is necessary. In this study we aimed to design a bioimpedance measurement setup to detect changes in venous segments after freezing-thawing cycles in a noninvasive manner. APPROACH: A bioimpedance spectroscopy measurement technique with a two-electrode setup was employed to monitor ovine jugular vein segments after each cycle during a process of seven freezing-thawing cycles. MAIN RESULTS: The results demonstrated changes in the impedance spectra of the measured venous segments after each freezing-thawing cycle. SIGNIFICANCE: This indicates that bioimpedance spectroscopy has the potential to be developed into a novel method for non-invasive and non-destructive monitoring of the viability of complex tissue after cryopreservation.

In vivo characterization of ischemic small intestine using bioimpedance measurements.

The standard clinical method for the assessment of viability in ischemic small intestine is still visual inspection and palpation. This method is non-specific and unreliable, and requires a high level of clinical experience. Consequently, viable tissue might be removed, or irreversibly damaged tissue might be left in the body, which may both slow down patient recovery. Impedance spectroscopy has been used to measure changes in electrical parameters during ischemia in various tissues. The physical changes in the tissue at the cellular and structural levels after the onset of ischemia lead to time-variant changes in the electrical properties. We aimed to investigate the use of bioimpedance measurement to assess if the tissue is ischemic, and to assess the ischemic time duration. Measurements were performed on pigs (n = 7) using a novel two-electrode setup, with a Solartron 1260/1294 impedance gain-phase analyser. After induction of anaesthesia, an ischemic model with warm, full mesenteric arterial and venous occlusion on 30 cm of the jejunum was implemented. Electrodes were placed on the serosal surface of the ischemic jejunum, applying a constant voltage, and measuring the resulting electrical admittance. As a control, measurements were done on a fully perfused part of the jejunum in the same porcine model. The changes in tan δ (dielectric parameter), measured within a 6 h period of warm, full mesenteric occlusion ischemia in seven pigs, correlates with the onset and duration of ischemia. Tan δ measured in the ischemic part of the jejunum differed significantly from the control tissue, allowing us to determine if the tissue was ischemic or not (P < 0.0001, F = (1,75.13) 188.19). We also found that we could use tan δ to predict ischemic duration. This opens up the possibility of real-time monitoring and assessment of the presence and duration of small intestinal ischemia.

Effects of stray capacitance to ground in three electrode monopolar needle bioimpedance measurements.

Positive phase angle is documented and analyzed in a three electrode monopolar needle measurement. Inductance equivalent behavior of the stray capacitance to ground is described as error source in a non-inductive sample measurement.

The development of a software program for analyzing spontaneous and externally elicited skin conductance changes in infants and adults.

OBJECTIVES: Changes in palmar and plantar skin conductance (SC) are due to outgoing bursts in the postganglionic efferent sympathetic cholinergic fibres, which responds to changes in central arousal state. The purpose of this study was designed to develop a software program for analyzing spontaneous and external elicited SC changes for infants and adults. METHODS: The program was designed to calculate the number and mean amplitude of the waves as well as the mean basal level in a given period. Different pre-set values for the minimum amplitude, maximum slope and minimum width of the spontaneous waves were used in the analysis program, and the results were compared with manually counted waves. The program was also used to perform coherent averaging of repeated elicited SC changes. For the mean elicited skin conductance responses, the latency time, response amplitude and recovery time were calculated. The habituation pattern could be calculated semi-automatically by analyzing each response. RESULTS: For SC waves, the minimum amplitude and the maximum slope should be, respectively, 0.02 microsiemens (microS) and 2 microS/s for infants and adults, and the width of the waves should be at least 1 s for adults, and unlimited for infants. The coherent average method was found to be a satisfactory method for revealing whether a subject responded to stimuli, and is recommended, especially for infants. CONCLUSIONS: Spontaneous and stimulated skin conductance are easily analyzed by this software program.

Line patterns in the mosaic electrical properties of human skin--a cross-correlation study.

A vehicle with 16 electrodes for the two-dimensional electrical admittance mapping of human skin is presented. Measurements on 20 test subjects have been carried out and analyzed for the possible detection of line patterns in the electrical properties of the skin, claimed to coincide with the so-called acupuncture meridian lines of ancient Chinese medicine. No such lines were found.

Dielectric properties of some keratinised tissues. Part 1: Stratum corneum and nail in situ.

Blister-skin and warts have been studied as possible sources of 'pure' stratum corneum without sweat ducts. The purpose of the study was to assess whether the DC electrical conductance measured on human skin is totally dominated by the sweat ducts, or is also significantly contributed to by the stratum corneum itself. By means of galvanic skin response (GSR) measurements, these tissues were found to be unrealiable as sources of 'pure' stratum corneum. This is because they displayed significant GSR waves, and hence should have some form of active pores. However, measurements on blister-skin and nail in situ revealed a substantial frequency independent electrical conductance at frequencies typically below 10 Hz.

Dielectric properties of some keratinised tissues. Part 2: Human hair.

Some electrical properties of human hair have been investigated to determine whether a significant DC electrical conductance is present in keratinised tissues. The DC conductance was found to be substantial and highly dependent on the moisture level in the hair fibres. At high moisture levels, the conductance was found to be almost frequency independent below 1 kHz. Absorption and desorption profiles were also monitored, revealing different stages of sorption mechanisms in the fibres. Although absorption was found to be a slow process with 'time constants' in the range of hours, desorption was much faster, in the range of a few minutes.

Comparison of four different FIM configurations--a simulation study.

Focused impedance measurements (FIM) are used in several fields, and address the problem of measuring the volume impedance of an object within a volume conductor. Several electrode configurations are possible, and these have different properties. Sensitivity fields of four configurations have been investigated. We present one new development of an existing FIM configuration, and we made finite element models of the configurations to analyse and compare them both graphically and numerically. The models developed have a variable-sized mesh that allows us to build complex models that fit easily in computer memory. We found that one configuration in particular, FIM4, was superior to the others in most aspects. We also analysed the effects of very high sensitivities in and under the electrodes. We found that even if the sensitivity is very high under the electrodes, the effects of inhomogeneities were not as high as one might expect.

Memristive model of electro-osmosis in skin.

We show that some of the nonlinear conductance properties of electro-osmosis in sweat-duct capillaries may be modeled by a memristive circuit. This includes both the observed phase shift and amplitude modulation of the electrical current response to a simple harmonic driving potential. Memristive sytems may therefore be expected to play a role in modeling the electrical properties of skin, and perhaps also in other systems where nonlinearities are observed in their bioimpedance.

A finite element model of needle electrode spatial sensitivity.

We used the finite element (FE) method to estimate the spatial sensitivity of a needle electrode for bioimpedance measurements. This current conducting needle with an insulated shaft was inserted in a saline solution and the current was measured at the neutral electrode. Model resistance and reactance were calculated and successfully compared with measurements on a laboratory model. The sensitivity field was described graphically based on these FE simulations.

Estimation of in vivo water content of the stratum corneum from electrical measurements.

In vivo water content in the epidermal stratum corneum can be estimated by means of low frequency susceptance measurements. In the in vitro calibration necessary to find the in vivo water content, the stratum corneum will have a uniform distribution of water across its thickness. However, in vivo stratum corneum has an increasing water concentration profile from the outermost towards the innermost parts. This paper will investigate the possibility of estimating the equilibrium water content in the in vivo stratum corneum non-invasively from electrical susceptance measurements. Given a known shape of the water concentration profile in the in vivo stratum corneum and the dependence of susceptance on the water content, it is possible to calculate the water content in vivo based on analytically derived expressions for the water concentration profile. A correspondence between in vivo and in vitro water content needed for this purpose is also established.

Facts and myths about electrical measurement of stratum corneum hydration state.

Some of the views presented in the chapter on 'Examination of stratum corneum hydration state by electrical methods' in Skin Bioengineering - Techniques and Applications in Dermatology and Cosmetology (Karger, 1998) are in strong disagreement with the results from basic research that has been conducted on skin impedance measurement over the last decades. This research has e.g. non-ambiguously shown that the frequency response of the stratum corneum does not obey the Cole equation and that measurement depth is strongly dependent on measurement frequency. One consequence of these findings is that multifrequency electrical measurements on stratum corneum are impossible to achieve in vivo with any electrode system known today. Hence, electrical measurements of stratum corneum hydration must be conducted at one single, low frequency.

Electrical methods for skin moisture assessment.

Skin sites on 8 test subjects were treated with moisturizers, and different electrical measuring methods were compared regarding their quality in the assessment of the induced changes in the stratum corneum hydration level. Low frequency susceptance measurements were found preferable to high frequency admittance measurements, and the advantages of monopolar measurements with the three-electrode system are described.

The Microfiltrometer (MicroFM): a new filtration device for the assessment of less deformable erythrocyte subpopulations.

The hardware of a new filtration device, the Microfiltrometer (MicroFM), is described. The different components of the device; impedance meter, power supply, measuring cell and its 5-micron Oligopore filter are described and it is shown how they are interrelated and interfaced to a computer for data acquisition. The properties of the filter and the general functioning principle of the device are also elucidated. For each run, the MicroFM generates elementary signals from individual passages of many hundreds of red blood cells (RBCs) through micropores of a given 5-micron Oligopore filter. Analysis of each elementary signal provides two complementary parameters, the transit time tau of the explored RBC and the change in electrical impedance deltaZ caused by the temporary flow of the considered RBC through a particular micropore of the filter. These two parameters can be utilized for reliable assessment of erythrocyte deformability on a cellular level.

Basic principles for evaluation of less deformable erythrocyte subpopulations with the Microfiltrometer.

The Microfiltrometer consists of a filtration system for diluted erythrocyte suspensions, through a filter containing 30 cylindrical micropores, 5 microm in diameter, under the influence of a driving pressure. A feeding sinusoidal alternating current of 40 kHz, 300 microA is delivered to the filter. The change in impedance is collected for each temporary flow of erythrocytes through a given micropore. Two main parameters are measured for individually explored erythrocytes: the entry time tau in the micropore and the maximal variation of impedance deltaZ occurring for the transitory flow. The slope deltaZ/tau defines the velocity of pore blockage. A "Microfiltrometer Deformability Index" (MDI) is established by using this slope. When MDI > or = 1, the erythrocyte is considered to be deformable and, conversely, when MDI < 1, the erythrocyte is considered to be undeformable. Using this procedure, less than 2% undeformable erythrocytes in healthy blood samples are identified, with a specificity of 99% and a sensitivity of 97.5%.